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Systemic sclerosis (SSc) is characterized by a complex interplay of vascular damage, inflammation, and fibrosis, affecting the skin and internal organs. Plasminogen activator inhibitor-1 (PAI-1), a protein encoded by the SERPINE1 gene, is a potential biomarker of SSc because it is primarily involved in fibrinolysis and is associated with the severity of some autoimmune diseases. This study aimed to determine the association between SERPINE1 variant -675 4G/5G and soluble PAI-1 (sPAI-1) levels with the clinical characteristics and risk of SSc in a Mexican population. This cross-sectional study included 56 SSc patients and 114 control subjects (CSs). The variant was genotyped via the PCR-RFLP method and the levels of sPAI-1 were determined using enzyme-linked immunosorbent assays (ELISAs). The -675 4G/5G variant was not associated with SSc risk or sPAI-I levels. However, higher sPAI-1 levels were observed in SSc patients than in CSs (p = 0.045); these levels were significantly correlated with age, platelets, glucose, and serum levels of transforming growth factor (TGF)-ß1, 2, and 3. The SERPINE1 -675 4G/5G variant did not show any association with SSc risk or sPAI-I levels. However, our study shows a possible alteration of sPAI-1 in this disease, which could be associated with the fibrotic and thrombotic processes in SSc.
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To achieve global herd immunity, widespread vaccination is the most effective strategy. Vaccines stimulate the immune system, generating cytokines and chemokines, isotype antibodies, and neutralizing antibodies; all these molecules collectively provide a more comprehensive characterization of the immune response post-vaccination. We conducted a longitudinal study in northwestern Mexico, involving 120 individuals before vaccination and after the first dose of the SARS-CoV-2 vaccine, and 46 individuals after their second dose. Our findings reveal that antibody levels stabilize over time; cytokine levels generally increase following the first dose but decrease after the second dose and higher than normal levels in IgG1 and IgG3 concentrations are present. Most of the innate cytokines determined in this study were higher after the first dose of the vaccine. Regardless of previous infection history, this finding suggests that the first dose of the vaccine is crucial and may stimulate immunity by enhancing the innate immune response. Conversely, increased levels of IL-4, indicative of a Th2 response, were found in individuals without prior exposure to the virus and in those vaccinated with CoronaVac. These results suggest that the immune response to COVID-19 vaccines is multi-faceted, with preexisting immunity potentiating a more robust innate response. Vaccine type plays a critical role, with genetic vaccines favoring a Th1 response and inactivated vaccines like CoronaVac skewing toward a Th2 profile.
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Anticuerpos Neutralizantes , Anticuerpos Antivirales , Vacuna BNT162 , Vacunas contra la COVID-19 , COVID-19 , ChAdOx1 nCoV-19 , Citocinas , SARS-CoV-2 , Humanos , COVID-19/inmunología , COVID-19/prevención & control , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Masculino , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Citocinas/inmunología , Femenino , Adulto , Persona de Mediana Edad , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Vacuna BNT162/inmunología , Vacuna BNT162/administración & dosificación , México , Estudios Longitudinales , ChAdOx1 nCoV-19/inmunología , ChAdOx1 nCoV-19/administración & dosificación , SARS-CoV-2/inmunología , Células Th2/inmunología , Células TH1/inmunología , Inmunoglobulina G/sangre , Vacunación , Vacunas de Productos Inactivados/inmunología , Vacunas de Productos Inactivados/administración & dosificación , Adulto Joven , AncianoRESUMEN
Background: Respiratory tract infections remain among the leading causes of mortality worldwide. The COVID-19 pandemic has highlighted the importance of mucosal immunity in defending against infectious agents. Vitamin A is known to influence the production of secretory immunoglobulin A (SIgA) predominantly in the gut, where it is a critical component of the first line of defense on mucosal surfaces. Methods: This cross-sectional study, conducted 14 days post-positive COVID-19 diagnosis, aimed to determine the relationship between the nutritional status of vitamin A and SIgA levels in COVID-19 outpatients. Serum and saliva samples were collected. Vitamin A nutritional status was determined based on the assessment of dietary intake and the analysis of retinol-binding protein 4 (RBP4). SIgA levels were analyzed from salivary samples. In addition, serum antibodies were analyzed. Results: Dietary vitamin A intake and RBP4 levels positively correlated with SIgA. Patients with higher vitamin A intake showed higher SIgA/IgG1 and SIgA/IgG3 ratios, while those with higher RBP4 levels showed higher SIgA/IgM, SIgA/IgG1, and SIgA/IgG2 ratios. Conclusions: These findings underscore a significant correlation between vitamin A nutritional status and SIgA levels in COVID-19 outpatients, which may suggest the potential importance of maintaining optimal vitamin A levels for the prevention of viral infections.
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Rheumatoid Arthritis (RA) is a multifactorial autoimmune disease. Currently, several genes play an important role in the development of the disease. The objective was to evaluate the association of the STAT4 rs7574865 and rs897200 gene variants with RA susceptibility, DAS28, RF, and anti-CCP in Western and Southern Mexico populations. Genotyping was performed on 476 samples (cases = 240; controls = 236) using the Taqman® system and qPCR probes. Disease activity was assessed using DAS28 and HAQ DI. CRP, ESR, RF, and anti-CCP were determined for clinical assessment. Our study showed there is a statistically significant association with susceptibility to RA for the rs7574865 variant in the Western population for the GT and TT genotypes. The same genotypes also showed a moderate-to-high activity according to DAS28 and positive anti-CCP compared to the control group. This association was not found in the Southern population. This work confirms the association of the rs7574865 variant with RA, as well as a moderate-to-high activity and positive anti-CCP in the Western population but not in the Southern population. No association of the rs897200 variant was found in any of the studied populations.
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Anticuerpos Antiproteína Citrulinada , Artritis Reumatoide , Humanos , México , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple/genética , Artritis Reumatoide/genética , Factor de Transcripción STAT4/genéticaRESUMEN
Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus that causes coronavirus disease 2019 (COVID-19). It is estimated that more than half of new infections are transmitted by asymptomatic people; therefore, the isolation of symptomatic people is not enough to control the spread of the disease. Methods: A total of 171 unvaccinated young adults (18-35 years) from Sonora, Mexico, who underwent a structured survey to identify prior COVID-19 infections, were included in this study. A qualitative determination of anti-SARS-CoV-2 antibodies in serum was performed by lateral flow immunoassay (Certum IgG/IgM Rapid Test™ cassette kit) and neutralizing antibodies were also determined (GenScript cPass assay). Results: A total of 36 people reported a history of COVID-19 infection, and 135 reported no history of COVID-19. In contrast, 49.6% (67/135) of individuals who had not reported a previous SARS-CoV-2 infection were seropositive to the rapid anti-SARS-CoV-2 antibody test, and 48.1% (65/135) of them had neutralizing antibodies. Conclusions: These results suggest that in young adults, SARS-CoV-2 infections could be asymptomatic in a high percentage of individuals, which could contribute in part to the slow control of the current pandemic due to the large number of asymptomatic cases that are contagious and that could be a silent spread of the virus.
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INTRODUCTION: Cytokine levels are related to the aethiopathogenia of acute apical abscesses (AAA); however, the specific cytokine profiles in these cases are unclear. This study aimed to investigate the changes in systemic cytokine levels in patients with AAA and trismus onset, postantibiotic treatment, and postroot canal disinfection. METHODS: In total, 46 AAA patients with trismus and 32 control subjects were included. After seven days of antibiotic therapy, root canal disinfection was performed in the AAA patients. The serum levels of cytokines were evaluated at basal, seven, and 14 days after endodontic treatment. Quantification of cytokines from T helper (Th) 1, Th2, Th17, and regulatory T cells profiles was determined using the BioPlex MagPix system, and the obtained data were analyzed using SPSS statistical software (P < .05). RESULTS: AAA patients showed higher tumor necrosis factor-alpha (TNF-α), interleukin (IL) -6, and IL-10 levels than control subjects, at basal measurement (P < .05); there were similar levels of interferon gamma, IL-1ß, IL-4, and IL-17 between groups (P > .05). IL-6 and IL-10 levels decreased after antibiotic treatment (P < .05), which was also associated with clinical improvement in patients with AAA and trismus. Patients with AAA had a positive correlation with higher serum levels of IL-6 and IL-10. In addition, TNF-α levels decreased only after antibiotic and endodontic treatment. CONCLUSIONS: In conclusion, patients with AAA had increased systemic serum levels of TNF-α, IL-6, and IL-10. Moreover, increased levels of IL-6 and IL-10 are associated with acute inflammatory symptoms. However, IL-6 and IL-10 levels decreased after antibiotic treatment, while TNF-α levels decreased after antibiotic and endodontic treatment.
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Citocinas , Absceso Periapical , Humanos , Interleucina-10 , Interleucina-6 , Factor de Necrosis Tumoral alfa , Absceso , TrismoRESUMEN
Systemic Sclerosis (SSc) is a chronic autoimmune disease characterized by immune disorder, microvascular damage, and fibrosis. TGFB1 gene encodes for the transforming growth factor isoform 1 (TGF-ß1), one of the most important pro-fibrotic cytokines. Therefore, variants in TGFB1 and changes in its expression could be associated with the pathogenesis of SSc. We aimed to evaluate the association of TGFB1 variants (+ 869T>C [rs1982073] and + 915G > C [rs1800471]) with the TGFB1 mRNA expression and SSc risk in the Southern Mexican population. We included 56 SSc patients and 112 control subjects (CS). The genetic variants were determined by the PCR-RFLP method. The TGFB1 mRNA expression was determined by qPCR. For the + 869T>C variant, the C allele was associated with SSc risk (OR = 1.733; CI = 1.087-2.762; p = 0.020). The C allele for the + 915G>C variant was also associated with SSc risk (OR = 11.168; CI = 1.289-96.754; p = 0.023). The relative expression of TGFB1 mRNA was 1.77-fold lower in SSc patients than in CS. Carriers of polymorphic alleles (TC or CC genotypes) for the + 869T>C variant showed 3.7-fold lower mRNA expression than the TT genotype in patients and 4.81-fold lower in CS. For the + 915G>C variant, patients with GA genotype had 1.78-fold lower mRNA expression than GG genotype carriers. In conclusion, the present study showed that + 869T>C and + 915G>C variants could be SSc risk factors for patients from Southern Mexico, and these genetic variants could induce lower mRNA expression of TGFB1.
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Esclerodermia Sistémica , Factor de Crecimiento Transformador beta1 , Humanos , Factor de Crecimiento Transformador beta1/genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Genotipo , Esclerodermia Sistémica/genética , Frecuencia de los GenesRESUMEN
Helicobacter pylori promotes the secretion of cytokines that regulate inflammation and carcinogenesis. Immune cells secrete cytokines into the extracellular medium or packaged in exosomes. The objective of this study was to analyze the profile of soluble and exosomal cytokines that were secreted by human peripheral blood mononuclear cells (PBMCs) that were infected with H. pylori and to build a network of interaction between cytokines and cellular proteins. PBMCs were obtained by density gradient centrifugation and infected with H. pylori for 24 h. The infection was verified by immunofluorescence and Western blot for CagA. The exosomes were obtained from culture supernatant by ultracentrifugation and characterized by transmission electron microscopy, particle size analysis, and Western blot for CD9 and CD81. Cytokines were quantified using a multiplex immunoassay in the culture supernatant, intact exosomes, and lysed exosomes. H. pylori adheres to lymphocytes and translocates CagA. In PBMCs, H. pylori induces an increase in the soluble and exosomal IL-1ß, IL-6, TNF-α, IL-10, IL-17A, IL-21, and IL-22. The protein-protein interaction (PPI) network shows that soluble and exosomal cytokines interact with proteins that participate in signaling pathways such as NF-κB, MAPK, PI3K-Akt, Jak-STAT, FoxO, and mTOR, that are related to carcinogenesis; moreover, TNF-α had the highest number of interactions. Cytokine-loaded exosomes represent another means of intercellular communication that is activated by H. pylori to stimulate inflammation, carcinogenesis, or cancer progression. Cytokine-loaded exosomes are likely to be associated with extragastrointestinal diseases of inflammatory origin.
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Infecciones por Helicobacter , Helicobacter pylori , Carcinogénesis/metabolismo , Citocinas/metabolismo , Mucosa Gástrica/metabolismo , Infecciones por Helicobacter/metabolismo , Helicobacter pylori/metabolismo , Humanos , Inflamación/metabolismo , Leucocitos Mononucleares/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
This study aimed to summarize the epidemiological and clinical characteristics of COVID-19 from Western Mexico people during 2020. A retrospective analysis from an electronic database of people visiting a sentinel center for molecular SARS-CoV-2 confirmatory diagnosis by RT-PCR from April to December 2020 was carried out for epidemiological and clinical description of COVID-19. Out of 23,211 patients evaluated, 6918 (29.8%) were confirmed for SARS-CoV-2 infection (mean age 38.5 ± 13.99), mostly females (53.8%). Comorbidities, such as diabetes (34.7%), obesity (31.15%), and hypertension (31.8%), presented an increased odds OR = 1.27, CI = 1.14-1.41; OR = 1.08, CI = 1.01-1.16; and OR = 1.09, CI = 0.99-1.19, respectively, for viral-infection. Moreover, fever, headache, and dry cough were the most frequent symptoms. No infection difference among sex was found. Those patients >60 years old were prone to COVID-19 severity (OR = 3.59, CI = 2.10-6.14), evaluated by the number of manifested symptoms, increasing with age. In conclusion, a high SARS-CoV-2 prevalence was found in Western Mexico. Comorbidities were frequent in infected people; nevertheless, no association with disease outcomes was observed, in contrast with the highest disease severity risk found in older patients; however, continuous monitoring should be carried since comorbidities have been reported as aggravating factors. This study can help the health officials for the elaboration of planning efforts of the disease management and others in the future.
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COVID-19 , SARS-CoV-2 , Adulto , Anciano , Femenino , Humanos , Masculino , México/epidemiología , Persona de Mediana Edad , Pandemias , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: Macrophage inhibitory factor (MIF) is a pro-inflammatory cytokine secreted by several cells, including those in the immune system and the skin. The MIF gene contains the SNP -173 G> C and STR -794 CATT5-8 polymorphisms in the promoter region capable of affecting its activity. Our objective was to investigate the MIF polymorphisms as a risk factor for plaque psoriasis (PP) in the Mexican population. METHODS: We genotyped both MIF polymorphism (rs5844572 and rs755622) in 224 PP patients with a clinical and histopathological diagnosis and 232 control subjects (CS) by the PCR-RFLP method. MIF serum levels were determined by an ELISA kit. RESULTS: We found significant differences in the genotypic and allelic frequencies for the MIF -173 G>C polymorphism; carriers of the GC genotype (OR 1.51, 95% CI 1.026-2.228, p = 0.03) and the C allele (OR 1.34, 95% CI 1.005-1.807, p = 0.04) had higher odds to present with PP. Moreover, the 6C haplotype was associated with PP risk (OR 2.10, 95% CI 1.22-3.69, p < 0.01). Also, the -173 CC genotype was associated with high MIF serum levels (p < 0.05). CONCLUSIONS: The -173 GC genotype and the 6C haplotype of the MIF polymorphisms are associated with susceptibility to PP in the Mexican population.
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Predisposición Genética a la Enfermedad/genética , Oxidorreductasas Intramoleculares/genética , Factores Inhibidores de la Migración de Macrófagos/genética , Polimorfismo de Nucleótido Simple/genética , Psoriasis/epidemiología , Psoriasis/genética , Adulto , Estudios de Casos y Controles , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Rheumatoid arthritis (RA) is an autoimmune inflammatory joint disease with complex pathogenesis associated with cytokine dysregulation. Macrophage migration inhibitory factor (MIF) plays a role in systemic inflammation and joint destruction in RA and could be associated with the secretion of other immune-modulatory cytokines such as IL-25, IL-31, and IL-33. For the above, our main aim was to evaluate the IL-25, IL-31, and IL-33 secretion from recombinant human MIF (rhMIF)-stimulated peripheral blood mononuclear cells (PBMC) of RA patients. The rhMIF and lipopolysaccharide (LPS) plus rhMIF stimuli promote the secretion of IL-25, IL-31, and IL-33 (p < 0.05) from PBMC of RA patients. The study groups, the different stimuli, and the interaction between both showed a statistically significant effect on the secretion of IL-25 (p < 0.05) and IL-31 (p < 0.01). The study of the effect of the RA patient treatments and their interaction with the effect of stimuli did not show an interaction between them. In conclusion, our study generates new evidence for the role of MIF in the secretion of IL-25, IL-31, and IL-33 and its immunomodulatory effect on RA.
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Artritis Reumatoide/inmunología , Artritis Reumatoide/metabolismo , Interleucina-17/metabolismo , Interleucina-33/metabolismo , Interleucinas/metabolismo , Oxidorreductasas Intramoleculares/metabolismo , Leucocitos Mononucleares/metabolismo , Factores Inhibidores de la Migración de Macrófagos/metabolismo , Adulto , Femenino , Humanos , Inmunomodulación/efectos de los fármacos , Oxidorreductasas Intramoleculares/farmacología , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/inmunología , Factores Inhibidores de la Migración de Macrófagos/farmacología , Masculino , Persona de Mediana Edad , Proteínas Recombinantes/farmacologíaRESUMEN
Macrophage migration inhibitory factor (MIF) significantly contributes to rheumatoid arthritis (RA) pathogenesis. We aimed to evaluate the canonical (CD74/CD44) and non-canonical MIF receptors (CXCR2,4 and 7) expression and sCD74 to establish their association with RA clinical activity according to DAS28-ESR. METHODOLOGY: 101 RA patients with different clinical activities (remission (n = 27), low (n = 16), moderate (n = 35) and high (n = 23)) and 9 control subjects (CS) were included. Expression was evaluated by flow cytometry and levels of soluble CD74 (sCD74) by ELISA. Data analysis was performed with FlowJov10.0, STATAv12.0, and GraphPad Prism v7.0. RESULTS: According to disease activity, CXCR7 expression (percentage of expression and mean fluorescence intensity (MFI)) was higher in granulocytes from patients in remission, while the expression of CXCR4 was higher in patients with high disease activity (p < 0.05). The expression of CD74 was higher in B cells (p < 0.05) and monocytes (p < 0.01) from patients in remission. Regarding sCD74 levels these were higher in patients with high disease activity when compared to those in remission (p <0.05). CONCLUSIONS: The results support the need for further study of the role of sCD74 as a soluble MIF decoy receptor, sequestering it to negatively regulate MIF signaling though its membrane receptors. The expression patterns of CXCR4 and CXCR7 show that the latter is a scavenger-type receptor that prevents endocytosis and even degradation of CXCR4 under inflammatory conditions.
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The inflammatory process implicates homeostasis disruption and increased production of inflammatory mediators. Myeloid differentiation primary response 88 (MyD88) is an essential protein recruited after lipopolysaccharide (LPS) and interleukin (IL)-1ß stimulation, a process that converges in nuclear factor kappa B (NF-κB) activation, as well as a transcription of several genes of both pro- and anti-inflammatory cytokines. The inhibition of MyD88 has shown efficacy by decrease inflammatory response, and has demonstrated potential application as a therapeutic target in chronic diseases. In this study, we investigate the effect of MyD88 dimerisation inhibitor ST2825 on cytokine production from rhIL-1ß and LPS-stimulated peripheral blood mononuclear cells (PBMC) from healthy blood donors (HBD). ST2825 significantly downregulates the production of IFN-γ, IL-6, IL-12, IL-2, IL-15, IL-7, VEGF, IL-1Ra, IL-4, IL-5, IL-13 and IL-9 (p < 0.05) in LPS-stimulated PBMC. Moreover, ST2825 had a relatively low impact on IL-1ß signalling pathway inhibition, showing that only a few specific cytokines, such as IFN-γ and IL-1Ra, are inhibited in rhIL-1ß-stimulated PBMC (p < 0.01). In conclusion, MyD88 dimerisation inhibitor ST2825 showed high efficacy by inhibiting pro- and anti-inflammatory cytokine production in LPS-stimulated PBMC. Moreover, although rhIL-1ß induced a sustained cytokine production (p < 0.05), ST2825 did not show a significant effect in the secretion of neither pro- nor anti-inflammatory cytokines in rhIL-1ß-stimulated PBMC.
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Regulación hacia Abajo/efectos de los fármacos , Compuestos Heterocíclicos con 2 Anillos/farmacología , Interleucina-1beta/metabolismo , Leucocitos Mononucleares/efectos de los fármacos , Lipopolisacáridos/farmacología , Factor 88 de Diferenciación Mieloide/química , Multimerización de Proteína/efectos de los fármacos , Compuestos de Espiro/farmacología , Antiinflamatorios/farmacología , Relación Dosis-Respuesta a Droga , Humanos , Inflamación/metabolismo , Leucocitos Mononucleares/metabolismo , Estructura Cuaternaria de ProteínaRESUMEN
Periodontitis is modulated by a complex dysbiotic microbiota, these species stimulate upward the production of pro-inflammatory cytokines such as TNF-α, which, in turn, upregulates the production of bone resorption molecules. Enzymes such as MMP-8 and 9 have been associated with the destructive disease. This study evaluated the composition of periodontal microbiota with the checkerboard hybridization technique and its correlation with TNF-α, MMP-8, and MMP-9 evaluated with ELISA, of 80 patients (45 healthy, and 35 with chronic periodontitis). The frequency of the 18 species evaluated was higher in patients with bone loss compared with control group. TNF-α in gingival crevicular fluid was significantly higher in bone loss group (p < 0.01); MMP-8 (p = 0.34) by MMP-9 (p < 0.05) in bone loss group obtained lower values than in control group. Positive correlation of TNF-α was obtained with Aggregatibacter actinomycetemcomitans (rho = 0.38; p < 0.01), Fusobacterium nucleatum (rho = 0.25; p < 0.05) and Porphyromonas gingivalis (rho = 0.26; p < 0.05); negative correlation of MMP-8 with A. actinomycetemcomitans (rho = 0.26; p < 0.01), Capnocytophaga sputigena (rho = 0.33; p < 0.01), and F. nucleatum (rho = 0.21; p < 0.05); also negative correlation of MMP-9 with F. nucleatum (rho = 0.23; p < 0.05), P. gingivalis (rho = 0.23; p < 0.05), and Tannerella forsythia (rho = 0.26; p < 0.01). TNF-α increased due to the increase in each count of A. actinomycetemcomitans (ß = 0.57; p = 0.00). The presence of A. actinomycetemcomitans (ß = 1.88; p = 0.00), Campylobacter rectus (ß = 0.78; p = 0.01), F. nucleatum (ß = 0.65; p = 0.04), and P. gingivalis (ß = 0.65; p = 0.04) significantly increases TNF-α levels. TNF-α in gingival crevicular fluid, despite the minimal amounts collected, is a good biomarker of periodontal disease; since levels of TNF-α increases with the increase of the most harmful species to the periodontium.
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Líquido del Surco Gingival , Microbiota , Humanos , Metaloproteinasa 8 de la Matriz , Metaloproteinasa 9 de la Matriz , Porphyromonas gingivalis , Prevotella intermedia , Factor de Necrosis Tumoral alfaRESUMEN
INTRODUCTION: Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial membrane damage and autoantibody production. RA is a heterogeneous disease, where cytokines such as IL-15, IL-21, and IFN-γ have been associated. However, their association with the autoantibodies has not been clearly described. The aim of this study was to evaluate the relationship between the cytokines IL-15, IL-21, and IFN-γ with the autoantibodies (RF, anti-CCP, anti-MCV, and anti-PADI4) in RA and disease activity. METHODOLOGY: This study included 153 RA patients and 80 control subjects (CS). The levels of IL-15, IL-21, IFN-γ, anti-CCP, anti-MCV, and anti-PADI4 were quantified by ELISA, whereas RF was quantified by turbidimetry. The disease activity was evaluated by the indices disease activity score 28-erythrocyte sedimentation rate (DAS28-ESR), clinical disease activity index (CDAI), and simple disease activity index (SDAI). RESULTS: The serum levels of IL-15, IL-21, and IFN-γ, and autoantibodies were increased in RA patients, compared with CS (p < 0.05). A correlation was found between IL-21 and anti-CCP and anti-MCV (p < 0.05). According to RA evolution, RF, anti-CCP, and anti-MCV had higher levels in early RA. In addition, increased levels of IL-21 were observed in RA seropositive patients (RF/anti-CCP/anti-MCV). The higher levels of both cytokines and autoantibodies were observed in moderate activity, evaluated by the three indices. CONCLUSIONS: Our results suggest that the increased soluble levels of IL-15, IL-21, and IFN-γ are involved in the inflammatory network in RA. However, IL-21 serum levels are associated with higher titers of autoantibodies (RF, anti-CCP, and anti-MCV) and IL-15 with moderate activity. Key Points ⢠IL-15, IL-21, and IFN-y are associated with the immunopathology of RA, but not significantly with the evolution of the disease. ⢠RF, anti-CCP, and anti-MCV had higher levels in early than established RA. ⢠IL-21 has an association with RF, anti-CCP, and anti-MCVand, for this reason, could be proposed as a disease biomarker. ⢠Patients with activity moderate of disease showed higher levels of RF, anti-CCP, anti-MCV, and IL-15.
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Artritis Reumatoide/sangre , Autoanticuerpos/sangre , Citocinas/sangre , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
The predominance of the effector mechanisms by CD4 + T cells is a characteristic of inflammatory autoimmune diseases such as rheumatoid arthritis (RA). The CD40/CD40L costimulatory pathway contributes to these pathogenic mechanisms by promoting autoantibody production and inflammation. Aberrant expression of CD40 and CD40L in RA patients has been shown, the latter prevailing in females. However, contrasting results have emerged regarding the clinical associations of these findings. We determined the association of CD40 and CD40L expression with the clinical activity evaluated through DAS28 in RA patients. A total of 38 female RA patients and 10 age- and sex-matched control subjects were included. CD40 and CD40L mRNA expression was quantified by real-time qPCR, cell surface proteins were determined by flow cytometry, and protein soluble forms were determined by ELISA. The expansion of a CD4 + T cell subpopulation expressing CD40 was identified in the RA group. In addition, high frequencies of CD4 + CD40L + T cells expressing high levels of CD40L, increased levels of sCD40L and overexpression of CD40L mRNA were observed in these patients. Moreover, there was a gradual increase in CD40L when data were stratified according to DAS28, except for very active patients. No correlation was observed between the levels of mRNA, cell surface protein and soluble protein of CD40 and CD40L with the clinical features of RA patients. There is an altered expression of CD40L in female RA patients in association with clinical activity assessed by DAS28, these findings support the evidence that suggests CD40L as a marker of clinical activity.
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Artritis Reumatoide/inmunología , Antígenos CD40/genética , Antígenos CD40/metabolismo , Ligando de CD40/genética , Ligando de CD40/metabolismo , Adulto , Artritis Reumatoide/genética , Biomarcadores/metabolismo , Linfocitos T CD4-Positivos/inmunología , Estudios de Casos y Controles , Femenino , Humanos , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Regulación hacia ArribaRESUMEN
INTRODUCTION: Systemic sclerosis (SSc) is a complex autoimmune disease, characterized by microvascular lesions, autoimmunity, and fibrosis. It is suggested that MIF participates in the amplification of the proinflammatory process in SSc; moreover, the promoter polymorphisms - 794 CATT5-8 (rs5844572) and - 173G>C (rs755622) in the MIF gene have been associated with an increase in MIF serum levels in several autoimmune diseases. The aim of this study was to analyze the relationship of the - 794 CATT5-8 and - 173G>C MIF polymorphisms with mRNA expression, MIF serum levels, and the Th1/Th2/Th17 cytokine profile in SSc. MATERIALS AND METHODS: A case-control study was carried out that included 50 patients with SSc and 100 control subjects (CS). Both polymorphisms were genotyped by PCR and PCR-RFLP. MIF levels were measured by ELISA kit. The cytokine profile and the MIF mRNA expression were quantified by BioPlex MagPix system and real-time PCR, respectively. RESULTS: An association between the - 794 CATT7 and - 173*C MIF alleles and the 7C haplotype with SSc susceptibility was found (p < 0.05). Also, the 7C haplotype was associated with increased MIF mRNA expression (p = 0.03) in SSc. In addition, an increase of IL-1ß and IL-6 serum levels in SSc patients was found as well as a positive correlation between MIF serum levels and Th1 and Th17 cytokine profiles. CONCLUSION: The MIF 7C haplotype is a susceptibility marker for SSc in the southern Mexican population and is associated with MIF mRNA expression. Moreover, there is a positive correlation between MIF serum levels and Th1 and Th17 inflammatory response in SSc.
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Citocinas/sangre , Oxidorreductasas Intramoleculares/genética , Factores Inhibidores de la Migración de Macrófagos/genética , Polimorfismo de Nucleótido Simple , Esclerodermia Sistémica/genética , Adulto , Biomarcadores/sangre , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad , Haplotipos , Humanos , Oxidorreductasas Intramoleculares/sangre , Factores Inhibidores de la Migración de Macrófagos/sangre , Masculino , México , Persona de Mediana Edad , Regiones Promotoras Genéticas , ARN Mensajero/genética , Esclerodermia Sistémica/sangre , Esclerodermia Sistémica/inmunología , Células TH1/inmunología , Células Th17/inmunología , Células Th2/inmunologíaRESUMEN
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by elevated levels of pro-inflammatory cytokines, such as interleukin (IL)-6, IL-17, and macrophage migration inhibitory factor (MIF). MIF induces IL-17 secretion and MIF promoter polymorphisms influence the expression of selected downstream mediators. The aim of this study was to investigate the relationship between known functional MIF haplotypes and Th17-related cytokine secretion profile in peripheral blood mononuclear cells (PBMC) from control subjects (CS) and RA patients stimulated with lipopolysaccharide (LPS) and recombinant human MIF (rhMIF). The -794 CATT5-8 and -173Gâ¯>â¯C polymorphisms of the MIF gene were determined by conventional PCR and PCR-RFLP, respectively. The most frequent haplotypes of the MIF polymorphism and PBMC were identified from three subjects homozygous for each haplotype and in both study groups, the PBMC were obtained and stimulated with LPS or rhMIF. The secretion of cytokines related to the Th17 profile was determined by a multiplex immunoassay (MAGPIX). LPS stimulation induced the secretion of cytokines related to the Th17 profile in PBMC from CS and RA patients, whereas, rhMIF only stimulated this response in PBMC from RA patients. PBMC from CS carriers of the MIF 7C haplotype showed more IL-17A, IL-17F, IL-22, and IL-23 secretion than non-7C carriers after LPS stimulation. In the case of rhMIF stimulation, the PBMC from CS carriers of the 7C haplotype secreted more IL-17A and IL-23 than non-7C carriers. In conclusion, genetic variants of the MIF promoter modulate the secretion of cytokines related to the Th17 profile in PBMC from CS inducing a differential response in comparison to PBMC from RA patients.
Asunto(s)
Artritis Reumatoide/genética , Citocinas/genética , Haplotipos/genética , Oxidorreductasas Intramoleculares/genética , Leucocitos Mononucleares/metabolismo , Factores Inhibidores de la Migración de Macrófagos/genética , Regiones Promotoras Genéticas/genética , Células Th17/metabolismo , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo Genético/genéticaRESUMEN
Introduction: Prolactin (PRL) is a 23-kDa protein that can be synthesized and secreted by pituitary and extrapituitary tissues such as immune cells due to its expression being regulated by two independent promoter regions. The promoter which is responsible for extrapituitary expression contains the single nucleotide polymorphism (SNP) -1149 G/T previously associated with autoimmune diseases in various populations. This study evaluates the relationship of PRL -1149 G/T polymorphism with PRL serum levels and clinical characteristics in systemic lupus erythematosus (SLE) patients from western Mexico. Material and methods: One hundred and sixty-three SLE patients classified according to the 1982 American College of Rheumatology (ACR) SLE classification criteria and 326 unrelated control subjects (CS), both from western Mexico, were included. The PRL -1149 G/T polymorphism was genotyped using the polymerase chain reaction restriction fragment length polymorphism technique, and both PRL serum levels and autoantibodies were measured by enzyme-linked immunosorbent assay (ELISA). Results: We found an association between the PRL -1149 TT genotype and SLE according to the recessive genetic model (OR = 2.26, 95% CI: 1.01-5.08, p = 0.04). The TT genotype was associated with anti-RNP antibodies (p = 0.04) and with higher scores of the Mex-SLEDAI (p = 0.02). Moreover, SLE patients showed elevated PRL serum levels (12.4 ng/ml; p < 0.01), and this condition was associated with renal activity and the presence of anti-RNP antibodies. Conclusions: PRL -1149 TT genotype is associated with susceptibility to SLE in a Mexican-Mestizo population, and high PRL serum levels are associated with anti-RNP antibodies and renal activity.
RESUMEN
BACKGROUND: Macrophage migration inhibitory factor (MIF) is an immunoregulatory cytokine that plays a crucial role as a regulator of the innate and adaptive immune responses and takes part in the destructive process of the joint in rheumatoid arthritis (RA) by promoting angiogenesis and inducing proinflammatory cytokines and matrix metalloproteinases (MMP). We evaluated if recombinant human MIF (rhMIF) induces the production of TNF-α, IFN-γ, IL-1ß, IL-6, IL-10, IL-17A, and IL- 17F in peripheral blood mononuclear cells (PBMC) from RA patients and control subjects (CS). METHODS: The PBMC from RA patients and CS were stimulated for 24 hours with combinations of LPS, rhMIF or the MIF antagonist ISO-1. Cytokine profiles were measured using a multiplex immunoassay and, macrophage migration inhibitory factor (MIF) was determined by ELISA kit. RESULTS: The PBMC of CS and RA produced Th1 and Th17 cytokines under stimulation with rhMIF, however, this effect was higher in the cells of RA patients. The rhMIFstimulated PBMC from RA patients produced higher levels of Th1 and Th17 cytokines in comparison with unstimulated cells: TNF-α (538.81 vs. 5.02 pg/mL, p<0.001), IFN-γ (721.90 vs. 8.40 pg/mL, p<0.001), IL-1ß (150.14 vs. 5.17 pg/mL, p<0.05), IL-6 (19769.70 vs. 119.85 pg/mL, p<0.001), IL-17A (34.97 vs. 0.90 pg/mL, p<0.01) and IL-17F (158.43 vs. 0.92 pg/mL, p<0.001). CONCLUSION: These results highlight the potential role of MIF in the establishment of the chronic inflammatory process in RA via Th1 and Th17 cytokine profile induction and provide new evidence of the role of MIF to stimulate the IL-17A and IL-17F expression in PBMC from RA and CS.