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OBJECTIVE: To evaluate the progression of coronary artery calcification (CAC) and associated risk factors in a systemic lupus erythematosus (SLE) cohort. METHODS: We reassessed the presence of CAC in patients with SLE who were screened 9 years before, using multidetector computed tomography. Clinical variables (cumulated disease activity and damage accrual), antiphospholipid syndrome and SLE serology, and cardiovascular (CV) risk factors (hypertension, BMI [kg/m2], modified Framingham risk score, lipid profile, menopausal status) were assessed longitudinally. RESULTS: We included 104 patients from the parent study. Most of them were women (94.2%), with a mean age of 41.0 (SD 8.3) years and mean disease duration of 14.8 (SD 2.9) years. We documented CAC in 17 patients (16.3%). Seven cases were from the parent study and 10 were incident cases. The cumulative incidence of CAC was 9% and the incidence density was 1 per 100 person-years. CAC occurred more frequently in the age groups 30-39 years and 40-44 years. All patients with previous CAC had worsening of their calcium indexes, and none developed clinical CV events. When comparing prevalent CAC cases (n = 17) vs patients without calcification (n = 87), both groups were similar in traditional CV risk factors, disease duration, Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) area under the curve (AUC), and Systemic Lupus International Collaborating Clinics (SLICC) score, but were more likely to be postmenopausal and have higher apolipoprotein B (apoB) levels. Patients with previous CAC had higher apoB levels, SLEDAI-2K AUC scores, and anticardiolipin IgG antibodies than incident cases. CONCLUSION: CAC in patients with SLE progressed over time but was not associated with adverse CV events during the first 9 years of follow-up. ApoB levels and postmenopausal status might be associated with this progression.

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TNFAIP3 is a classical systemic lupus erythematosus (SLE)-associated risk locus identified by genome-wide association studies (GWASs) and replicated by candidate gene association studies primarily in Caucasians and Asians. However, in Latin American populations, its role on SLE susceptibility is not known. We conducted a case-control study to evaluate whether the TNFAIP3 rs2230926T/G (Phe127Cys) variant is associated with risk of developing SLE in a cohort of Mexican patients. The TNFAIP3 rs2230926T/G variant was analyzed in 561 patients with SLE and 499 control subjects, using TaqMan probes. We found that the G allele was associated with susceptibility to SLE under the allelic (OR 2.09, p = 0.005) and genotypic (OR 2.14, p = 0.004) models. In conclusion, our results show that TNFAIP3 rs2230926T/G is a risk factor for the development of SLE in the Mexican population.

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OBJECTIVE: Variants in STAT4 are associated with systemic lupus erythematosus (SLE) and other autoimmune diseases. We undertook this study to investigate how disease-associated variants affect STAT4 expression, in particular in CD4+ T cells where STAT4 plays an essential role. METHODS: We compared Th1 differentiation between naive CD4+ T cells from healthy donors homozygous for the risk (R/R) or nonrisk (NR/NR) alleles. We analyzed epigenetic marks in STAT4 and evaluated the relevance of its third intron, assessed the consequences of Stat4 overexpression in vivo in mice, and analyzed the effects of the STAT4 genotype in patients with lupus nephritis. RESULTS: Naive CD4+ T cells from NR/NR healthy donors down-regulated STAT4 in response to interleukin-12 (IL-12). In contrast, cells from R/R healthy donors maintained high levels. R/R cells exhibited a higher abundance of transcriptionally active STAT4 and increased interferon-γ production. Accordingly, R/R healthy donors exhibited a stronger induction of local active enhancer marks. Genetic editing confirmed the presence of a negative regulatory region in the STAT4 third intron, where most of the SLE-associated STAT4 single-nucleotide polymorphisms (SNPs) are located. In vivo forced expression demonstrated that increases in Stat4 levels in T cells enhanced glomerulonephritis in mice. Accordingly, the R/R genotype was associated with suboptimal response to treatment and with worse clinical outcomes in patients with proliferative lupus nephritis. CONCLUSION: The SLE-associated STAT4 haplotype correlates with an abnormal IL-12-mediated STAT4 transcriptional regulation. Carriers of the risk variant exhibit exaggerated CD4+ proinflammatory capacities that, in the context of SLE, contribute to more severe disease. R/R patients may benefit from blockade of the IL-12/STAT4 pathway.

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OBJECTIVES: To characterize the clinical presentation and outcomes of LN in a Hispanic cohort from Mexico. METHODS: We studied 440 subjects with systemic lupus erythematosus and biopsy-proven LN followed for >36 months. We obtained demographic, clinical, laboratory, histopathological and treatment variables. All outcomes were analysed by survival analysis and included response to therapy, renal relapses, progression of kidney disease (decline in eGFR ≥ 30%, doubling of serum creatinine, end-stage kidney disease) and patient survival. RESULTS: The median age of the study cohort was 29 years (IQR 23-37) and 96% were female. The median eGFR at inclusion was 81 mL/min/1.73m2 (IQR 48-118) and 24 h-uPCR was 3.4 g/g (IQR 1.9-5.6). Mixed class LN (III/IV+V) was the most frequently observed (69%). Over a median follow-up of 79 months, complete response rates were 22.3%, 40.5% and 51.6%, at 6, 12 and 24 months, respectively. Renal relapse rates were 32.3% and 50.6% at 3 and 5 years. By 3 and 5 years, 20.7% and 31.4% had decline in eGFR ≥30%, 14.4% and 22.5% doubled their serum creatinine, and 9.1% and 17.7% progressed to ESKD. The factors associated with loss of kidney function were age, eGFR at presentation, the histologic chronicity index in the kidney biopsy, and the type of response to therapy. Patient survival was 98.2% and 97.1% at 3 and 5 years. CONCLUSION: Although the response to treatment and patient survival in this Latin American cohort is comparable to that observed in other regions, there is still a high rate of renal relapses and progression to decline in kidney function.

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BACKGROUND: Repeated renal flares in lupus nephritis (LN) have been associated with worse long-term kidney function. This study aimed to assess the impact of repeated LN flares in response to therapy, kidney and patient prognosis. METHODS: All patients from a biopsy-proven LN cohort between 2008 and 2018 were segregated into three groups according to the number of LN flares when they entered our cohort: first LN flare, second LN flare or third LN flare. The following outcomes were evaluated by unadjusted and adjusted time-to-event analyses: complete and partial response, disease relapses, progression to decline of 30% of the estimated glomerular filtration rate (eGFR), doubling of serum creatinine, end-stage kidney disease and patient survival. RESULTS: A total of 441 patients were included: 257 (58%) in their first LN flare, 102 (23%) in their second LN flare and 82 (19%) in their third LN flare. There were significant differences in LN flare presentation in age, eGFR, serum albumin, pyuria and hematuria among groups. The National Institutes of Health chronicity indices and the percentage of patients with vascular lesions were higher in groups at progressive LN flares. In the adjusted analyses, complete and partial response rates decreased, as well as kidney and patient survival, at a progressive number of LN flares. No differences in the dynamic course of all surveillance laboratory parameters were observed in the first year after initial therapy among LN flare groups. CONCLUSIONS: A progressive number of LN flares is associated with a lower response to therapy and an adverse prognosis for kidney function and patient survival.

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OBJECTIVES: The present study aims to assess the course of uMCP-1 and its association with response to therapy and long-term kidney function in a prospective cohort of adults who received a kidney biopsy for suspicion of active lupus nephritis (LN). METHODS: Subjects were segregated into a histologically active LN group and a histologically chronic LN group. Both groups were followed for > = 36 months and urine were collected at flare, 3, 6, and 12 months of follow-up. The association between the course of uMCP-1, response to treatment, and progression to 30% loss of the eGFR was evaluated by linear mixed models for repeated measures. RESULTS: A kidney biopsy was performed on 125 subjects. In 114, the report was consistent with histologically active LN; in 11, with histologically chronic LN. Urine MCP-1 levels were significantly higher in the active LN than in the chronic LN group. Urine MCP-1 levels correlated with the histological findings of cellular crescents, endocapillary hypercellularity, interstitial inflammation, glomerular sclerosis, interstitial fibrosis, and tubular atrophy. The mean estimates of uMCP-1 at flare were higher in the non-response group than in the complete response group, and decreased in the complete/partial response groups by the third month, while they remained elevated in the non-response group. The mean estimates for uMCP-1 were higher at LN flare and remained elevated in patients who progressed to loss of 30% of the eGFR, while they decreased in patients with stable kidney function. CONCLUSION: The first-year course of uMCP-1 is associated with response to therapy and kidney survival in LN. Key Points •Urine MCP-1 levels differentiate histologically-active lupus nephritis from histologically-chronic lupus nephritis •Urine MCP-1 levels decrease by 3 months of therapy in subjects with a favorable response whose kidney function remains stable long-term •Urine MCP-1 levels remain elevated during the first year of therapy in subjects the will later lose kidney function.

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OBJECTIVE: To determine the independent impact of different definitions of remission and low disease activity (LDA) on damage accrual. METHODS: Patients with ≥2 annual assessments from a longitudinal multinational inception lupus cohort were studied. Five mutually exclusive disease activity states were defined: remission off-treatment: clinical Systemic Lupus Erythematosus Disease Activity Index (cSLEDAI)-2K=0, without prednisone or immunosuppressants; remission on-treatment: cSLEDAI-2K score=0, prednisone ≤5 mg/day and/or maintenance immunosuppressants; low disease activity Toronto cohort (LDA-TC): cSLEDAI-2K score of ≤2, without prednisone or immunosuppressants; modified lupus low disease activity (mLLDAS): Systemic Lupus Erythematosus Disease Activity Index-2K score of 4 with no activity in major organ/systems, no new disease activity, prednisone ≤7.5 mg/day and/or maintenance immunosuppressants; active: all remaining visits. Only the most stringent definition was used per visit. Antimalarials were allowed in all. The proportion of time that patients were in a specific state at each visit since cohort entry was determined. Damage accrual was ascertained with the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). Univariable and multivariable generalised estimated equation negative binomial regression models were used. Time-dependent covariates were determined at the same annual visit as the disease activity state but the SDI at the subsequent visit. RESULTS: There were 1652 patients, 1464 (88.6%) female, mean age at diagnosis 34.2 (SD 13.4) years and mean follow-up time of 7.7 (SD 4.8) years. Being in remission off-treatment, remission on-treatment, LDA-TC and mLLDAS (per 25% increase) were each associated with a lower probability of damage accrual (remission off-treatment: incidence rate ratio (IRR)=0.75, 95% CI 0.70 to 0.81; remission on-treatment: IRR=0.68, 95% CI 0.62 to 0.75; LDA: IRR=0.79, 95% CI 0.68 to 0.92; and mLLDAS: IRR=0.76, 95% CI 0.65 to 0.89)). CONCLUSIONS: Remission on-treatment and off-treatment, LDA-TC and mLLDAS were associated with less damage accrual, even adjusting for possible confounders and effect modifiers.

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OBJECTIVE: In systemic lupus erythematosus (SLE), disease activity and glucocorticoid (GC) exposure are known to contribute to irreversible organ damage. We aimed to examine the association between GC exposure and organ damage occurrence. METHODS: We conducted a literature search (PubMed (Medline), Embase and Cochrane January 1966-October 2021). We identified original longitudinal observational studies reporting GC exposure as the proportion of users and/or GC use with dose information as well as the occurrence of new major organ damage as defined in the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. Meta-regression analyses were performed. Reviews, case-reports and studies with <5 years of follow-up, <50 patients, different outcomes and special populations were excluded. RESULTS: We selected 49 articles including 16 224 patients, 14 755 (90.9%) female with a mean age and disease duration of 35.1 years and of 37.1 months. The mean follow-up time was 104.9 months. For individual damage items, the average daily GC dose was associated with the occurrence of overall cardiovascular events and with osteoporosis with fractures. A higher average cumulative dose adjusted (or not)/number of follow-up years and a higher proportion of patients on GC were associated with the occurrence of osteonecrosis. CONCLUSIONS: We confirm associations of GC use with three specific damage items. In treating patients with SLE, our aim should be to maximise the efficacy of GC and to minimise their harms.

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ABSTRACT A renal biopsy is the 'gold standard' for diagnosis and classification of lupus nephritis (LN). The role of repeat renal biopsy in lupus nephritis (LN) to guide treatment or predict prognosis has been controversial. A systematic literature review was conducted based on retrospective and prospective studies. The studies were identified using English electronic scientific databases, including MEDLINE PUBMED, published between January 1990 and August 2020. The eligibility criteria were studies including adult LN patients with at least one follow-up renal biopsy with appropriate longitudinal information. Case reports, studies with incomplete information or including duplicate patients were excluded. Based on the inclusion and exclusion criteria, a total of 73 publications were identified. This study included a total of 1167 repeat biopsies in LN patients from 15 studies. The primary indication for a repeat biopsy was relapse in 44-78% of the cases, and lack of response in 13-51%. Additionally, several repeat biopsies were done according to the protocol, after induction and maintenance therapy. In terms of histopathological class switches, there was a higher frequency of changes from nonproliferative to proliferative lesions. Only two studies provide a definition of histological response. There were often changes in the therapeutic approach after a repeat biopsy. Repeat kidney biopsies are helpful in patients with LN flare/relapse, and in patients with poor treatment response. Histological transformation was a common finding. The histologic and clinical responses are discordant. A repeat biopsy could be of prognostic value for therapeutic decision-making.

RESUMEN La biopsia renal es el «estándar de oro¼ para el diagnóstico y la clasificación de la nefritis lúpica (NL). El papel de la biopsia renal repetida en nefritis lúpica para orientar el tratamiento o predecir el pronóstico ha sido controversial. Se llevó a cabo una revisión sistemática de la literatura basada en estudios retrospectivos y prospectivos. Los estudios se identificaron a través de bases de datos científicas electrónicas en inglés, incluyendo Medline PubMed, de publicaciones entre enero de 1990 y agosto del 2020. Los criterios de elegibilidad fueron estudios que incluyeran a pacientes adultos con NL, quienes tuvieran al menos una biopsia renal de seguimiento, con información longitudinal apropiada. Se excluyeron informes de casos, estudios con información incompleta o con pacientes duplicados. Basándose en los criterios de inclusión y exclusión, se identificaron 73 publicaciones. En la presente revisión se analizaron un total de 1.167 biopsias repetidas en pacientes con NL en 15 estudios. Las principales indicaciones para la biopsia repetida fueron: recidiva en 44-78% de los casos, y falta de respuesta en 13-51%. Adicionalmente, varias biopsias repetidas se hicieron conforme al protocolo, luego de la terapia de inducción y de mantenimiento. Con respecto a los cambios de clase histopatológica, hubo una mayor frecuencia de cambios de lesiones no proliferativas a lesiones proliferativas. Solamente dos estudios ofrecen una definición de respuesta histológica. Con frecuencia hubo cambios en el abordaje terapéutico después de realizar la biopsia repetida. Las biopsias renales repetidas son útiles en pacientes con exacerbación/recidiva y en pacientes con falta de respuesta a tratamiento. La transformación histológica fue un hallazgo frecuente; las respuestas histológicas y clínicas son discordantes. Una biopsia repetida puede ser de valor pronóstico para la toma de decisiones terapéuticas.

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ABSTRACT Systemic lupus erythematosus is a multisystemic autoimmune disorder that predominantly affects women in reproductive years. Pregnancy in women with SLE is still considered a high-risk condition although several strategies may improve maternal and fetal outcomes. Preconception counseling is fundamental and should include identification of risk factors for adverse pregnancy outcomes, explanation of potential maternal and obstetric complications and timely planning of pregnancy. Risk stratification must consider end-organ damage, comorbidities, disease activity and autoantibodies profile in order to implement an individual-risk pregnancy monitoring plan by a multidisciplinary team. Hydroxychloroquine and low dose aspirin have shown to lower the risk of disease flares and preeclampsia with a good safety profile, so its use during pregnancy in all SLE patients is recommended. Lupus nephritis and preeclampsia share clinical and laboratory features hindering differentiation between both entities. Novel angiogenic markers and fetal ultrasound findings could be helpful in the differential diagnosis, especially after 20 weeks of gestation. Antiphospholipid antibodies, particularly lupus anticoagulant, are closely associated with obstetric complications. Therapy with low dose aspirin and heparin, according to risk profile, may improve live birth rates. Anti-Ro/La antibodies confer risk for neonatal lupus, and therefore preventive therapy and special fetal surveillance should be instituted.

RESUMEN El lupus eritematoso sistémico es un trastorno autoinmune multisistémico que afecta primordialmente a mujeres en edad reproductiva. El embarazo en mujeres con LES aún se considera una condición de alto riesgo, a pesar de que diversas estrategias pueden mejorar los desenlaces maternos y fetales. La asesoría preconcepción es fundamental, y debe incluir la identificación de factores de riesgo de desenlaces adversos del embarazo, una explicación de las posibles complicaciones maternas y obstétricas, así como la planificación oportuna del embarazo. La estratificación de riesgos debe considerar el daño orgánico terminal, las comorbilidades, la actividad de la enfermedad y el perfil de autoanticuerpos, a fin de llevar a cabo un plan de monitoreo de los riesgos individuales del embarazo por parte de un equipo multidisciplinario. La hidroxicloroquina y la aspirina a bajas dosis han demostrado reducir el riesgo de exacerbaciones de la enfermedad y de preeclampsia, con un buen perfil de seguridad, por lo cual se recomienda su uso en todas las pacientes con LES durante el embarazo. La nefritis lúpica y la preeclampsia comparten características clínicas y de laboratorio, obstaculizando la diferenciación entre las 2 entidades. Nuevos marcadores angiogénicos y hallazgos ecográficos fetales pudieran ser de utilidad para el diagnóstico diferencial, especialmente después de las 20 semanas de gestación. Los anticuerpos antifosfolípidos, en particular el anticoagulante lúpico, tiene una estrecha asociación con las complicaciones obstétricas. El tratamiento con aspirina a bajas dosis y heparina, según el perfil de riesgos, puede mejorar las tasas de nacimientos vivos. Los anticuerpos anti-Ro/La representan un riesgo de lupus neonatal, por lo cual debe instituirse tratamiento preventivo y vigilancia fetal especial.

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INTRODUCTION: Kidney survival rates in lupus nephritis (LN) remain suboptimal, with 10-20% of patients progressing to end-stage kidney disease by 10-20 years. Recently, the landscape of LN management has changed with the advent of new molecules that have demonstrated safety and efficacy in clinical trials. AREAS COVERED: In this review, we approach the current state of LN management, the unmet therapeutic needs, and deep dive into voclosporin, a novel calcineurin inhibitor (CNI) that has demonstrated improved efficacy when added to a mycophenolate mofetil (MMF) and glucocorticoid regimen, without an increase in adverse events. We focus on the characteristics of this new CNI and the studies that led to its approval by the US FDA. EXPERT OPINION: Voclosporin adds to therapeutic options for LN. This drug offers potential advantages over other CNIs. The addition of voclosporin to a standard-of-care regimen of MMF/glucocorticoids demonstrated higher and faster response rates. As other regimens, a combination of CNI, MMF, and glucocorticoids must be individualized and is not appropriate for all patients. Some questions remain to be answered for this regimen, such as the length of treatment, the tapering schedule, and its long-term safety and efficacy for preserving kidney function.

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OBJECTIVE: To conduct a diagnostic assessment of pregnant women using a screening questionnaire for SLE. MATERIALS AND METHODS: This was an analytical cross-sectional study carried out at the National Institute of Perinatology between 1 November 2019 and 28 February 2020, using a screening questionnaire for SLE. Antinuclear antibody and anti-double stranded DNA antibody tests and a clinical assessment by a rheumatologist were conducted for participants who obtained ≥4 positive responses on the questionnaire. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the screening questionnaire for SLE were calculated. RESULTS: The questionnaire survey was conducted with 540 pregnant patients, 22 of whom (4.1%) had ≥4 positive responses. An antinuclear antibody test was conducted in all aforementioned 22 patients; 17 (77.3%) showed titres of ≥1:80. Of the 22 patients, 19 (86.4%) underwent clinical assessment by a rheumatologist. The patients were classified according to the SLE classification criteria: 7/19 (36.9%) met the revised 1997 American College Rheumatology (ACR) criteria, 8/19 (42.1%) met the Systemic Lupus International Collaborating Clinics criteria and 7/19 (36.9%) met the 2019 ACR/EULAR criteria (sensitivity=0.86, specificity=0.97, PPV=0.77 and NPV=1 for antinuclear antibody titre of ≥1:80; sensitivity=0.88, specificity=0.98, PPV=0.37 and NPV=1 for SLE according to the 2019 ACR/EULAR criteria). CONCLUSIONS: The questionnaire showed high sensitivity and specificity in the diagnosis of SLE. Given its usability and cost:benefit ratio, this strategy should be used for all patients coming in for their first visit to determine who requires antinuclear antibody testing and who needs to be referred to a rheumatologist.

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The AIRE gene influences the expression of a wide array of self-antigens in the thymus, and is essential to the negative selection of self-reactive T cells and establishment of central tolerance. Single nucleotide variants (SNVs) such as rs878081C/T (Ser196Ser) and rs2075876G/T at this locus have been associated with susceptibility to rheumatoid arthritis, mainly in Asian populations, but its role in systemic lupus erythematosus (SLE) has not been documented. We performed a case-control association study with 379 SLE patients and 460 controls from central Mexico. In addition, we replicated our finding in another group of 179 SLE patients and 97 controls from the same region of Mexico. In the first group, we identified that the AIRE Ser196Ser synonymous variant was associated with SLE (OR 1.4, p = 0.009), meanwhile, in the second group we observed the following: OR 1.7, p = 0.024. No association was found between these AIRE SNVs and lupus nephritis. Our results suggest that AIRE is a risk factor for SLE in our population. This study is the first to document an association between AIRE and SLE susceptibility.

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We compared the chemokine/receptor expression in skin biopsies of discoid (SLE/DLE) and subacute lupus (SLE/SCLE) and correlated it with tissue and circulating effector CD4 T cells/regulatory cells. Skin biopsies and peripheral blood from 9 active SLE/DLE patients, 9 SLE/SCLE patients, 5 control SLE patients without cutaneous lesions and 10 control healthy donors were included. Clinical skin activity was measured by Cutaneous Lupus Erythematosus Disease Area and Severity Index scoring, and systemic activity was measured by a modified SLEDAI-2K excluding the cutaneous items. Pain and pruritus were evaluated by a 10-point visual analogue scale. To determine the frequencies of CXCL-10/CXCR3-, CCL2/CCR2-, CCL17/CCR4-, CCL20/CCR6-, CCL27/CCR10-, CXCL8/CXCR1-, CXCL13/CXCR5-, IL-22-, CD4/IL-17A-, CD4/IL-4-, CD4/IFN-γ-, CD123/IDO-, CD25/Foxp3-, and CD20/IL-10-expressing cells, double immunostaining procedures were performed. Circulating CD4+/CD161-/IL-22+, CD4+/CD161+/IL-17+, CD4+/CD25-/IL-4+, CD4+/CD25-/IFN-γ+, CD4+/CD25hi/Foxp3+, CD3+/CD19+/CD38hi/IL-10+, and CD123+/CD196+/IDO + cells were analyzed by flow cytometry. RESULTS: In the tissue, CXCL10, CXCR5, and CCL20 expression and IL-22+, CD4+/IL-17+, CD4+/IFN-γ + and CD123+/IDO + cell percentages were increased in SLE/DLE versus SLE/SCLE. Circulating CD4+/CD161-/IL-22+, CD4+/CD161+/IL-17+, CD4+/CD25-/IFN-γ+, CD19+/CD38hi/IL-10 + and CD123+/CD196+/IDO + cell percentages were higher in SLE/DLE versus SLE/SCLE. In the tissue, we found positive correlations between CXCR3 and CD4+/IL-17 + cells; CCR2 and CD4+/IFN-γ + cells; and CCR10 and CD123+/IDO + cells in the SLE/DLE patients and between CXCL13 and CD20+/IL-10 + cells in the SLE/SCLE patients. In the peripheral blood, we determined positive correlations between CXCR5 and CD4+/CD25-/IFN-γ + cells; CCL17 and CD4+/CD161-/IL-22 + cells; and CCL17 and CD4+/CD161+/IL-17 + cells in the SLE/DLE patients and between CXCR5 and CD3+/CD19+/CD38hi/IL-10 + cells; CCR2 and CD4+/CD25hi/Foxp3 + cells; and CXCR1 and CD4+/CD25hi/Foxp3 + cells in the SLE/SCLE patients. Positive correlations between the pain score and the expression of CCL2 and CCR6 expression were found in the SLE/SCLE patients. In conclusion, the correlations between the expression of chemokines/receptors and subpopulations of effector/regulatory cells showed differential responses among the cutaneous pathologies.

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OBJECTIVE: To validate the association of thrombotic events with positive lupus anticoagulant (LA) and co-presence of anti-RNP/Sm, as well as the diagnostic accuracy of this combination of antibodies for thrombosis. METHODS: Case-control study of patients with systemic lupus erythematosus (SLE) who presented thrombosis after SLE diagnosis and controls with SLE without thrombosis. Comorbidities, traditional risk factors, clinical variables, and treatment were evaluated. Antiphospholipid (aPL) and anti-RNP/Sm antibodies were determined. RESULTS: Sixty-three cases and 63 controls were studied, 88% women, median age of 40 years, and disease duration of 135 months at study inclusion. No differences were found between groups regarding age, comorbidities, or clinical characteristics at SLE diagnosis. Patients with thrombosis were more frequently positive for anti-RNP/Sm (p = 0.001), IgG aCL (p = 0.02), IgG anti-B2GPI (p = 0.02), IgM anti-B2GPI (p = 0.02), LA (p < 0.001), the combination of anti-RNP/Sm + LA (p < 0.001), and aPL triple marker (p = 0.002), compared to controls. The combination of anti-RNP/Sm + LA, SLEDAI-2 K, and prednisone dose was associated with thrombosis (p < 0.05). The combination of anti-RNP/Sm + LA showed 56% sensitivity, 79% specificity, 73% positive predictive value, 64% negative predictive value, positive likelihood ratio (LR) 2.69, and negative LR 0.56 for predicting thrombosis. No difference was found in the comparison of area under the curve between LA alone and the combination of anti-RNP/Sm + LA (p = 0.73). CONCLUSION: Thrombosis was associated with disease activity, dose of prednisone, and the combination of anti-RNP/Sm antibodies and LA. This combination of antibodies could be useful in the identification of SLE patients at risk of thrombosis.

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To determine, among systemic lupus erythematosus patients, factors associated with active tuberculosis. We performed a case-control study, in a tertiary-care center in Mexico City. We defined cases as systemic lupus erythematosus patients with active tuberculosis and matched them 1:1 with systemic lupus erythematosus patients without tuberculosis (controls) by age, date of systemic lupus erythematosus diagnosis, and disease duration. We analyzed clinical variables, lupus disease activity (SLEDAI-2K), and accumulated damage (SLICC/ARC-DI). We performed a nonconditional logistic regression to determine factors associated with tuberculosis. We identified 72 tuberculosis cases among systemic lupus erythematosus patients, 58% were culture confirmed. Thirty-three percent (24/72) were pulmonary only, 47.2% (34/72) extrapulmonary only, and 19.4% both. After adjustment for age, gender, and socioeconomic status, SLEDAI-2K and SLICC/ARC-DI, a 1-year cumulative dose of prednisone ≥ 3 g (odds ratios (OR), 18.85; 95% confidence interval (95% CI), 6.91-51.45) was associated with tuberculosis, and the antimalarial treatment was protective (OR, 0.13; 95% CI, 0.04-0.36). Among systemic lupus erythematosus patients, cumulative dose of prednisone is associated with tuberculosis. Further research is required to elucidate the protective effect of antimalarial drugs for tuberculosis. Preventive strategies must be implemented in patients at risk.

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To evaluate the association of C-reactive protein (CRP) polymorphisms with risk of development SLE in a group of Mexican individuals. Five CRP polymorphisms (rs3093059, rs3093062, rs1800947, rs1130864, and rs1205) were determined by PCR-restriction fragment length polymorphism and SNP rs3093061 by refractory mutation system PCR assay in 126 SLE patients and 131 controls. Four of the polymorphisms showed differences between patients and controls. rs3093061 polymorphism was associated with a lower risk of developing lupus principally in the codominant 2 (OR = 0.219, 95% CI 0.108-0.785, P = 0.015) model. rs1130864 was associated with decreased risk mainly under codominant 1 (OR = 0.288, 95% CI 0.143-0.581, P = 0.001) model. rs1205 was associated under the over-dominant model (OR = 0.504, 95% CI 0.270-0.942, P = 0.032). The rs3091244 polymorphism was associated with decreased risk of SLE mostly under additive (OR = 0.605, 95% CI 0.393-0.931. P = 0.022) model. Our study establishes that rs3093061, rs1130864, rs1205, and rs3091244 polymorphisms are associated with decreased risk of developing SLE.

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OBJECTIVES: In 2004 and 1999, respectively, recent-onset rheumatoid arthritis (RA) and systemic lupus erythematous (SLE) cohorts were initiated; the 36 item Medical Outcome Study Short-Form survey (SF-36) was applied beginning from enrolment. The objectives were to compare the SF-36v2 scores between patients from both cohorts who achieved sustained remission and to define the role of disease diagnosis as associated to SF-36v2 normative data in remission patients. METHODS: Sustained remission was considered when RA and SLE patients achieved at least 12 months of continuous follow-up with either SLE disease activity index 2000 update =0 or Disease Activity Score (28 joints) ≤2.4, respectively. Up to December 2015, data from 172 RA patients and 211 SLE patients were reviewed. SF-36v2 scores were available for the totality of remission assessments. Logistic regression models were used to investigate factors associated with normative SF-36v2. Written informed consent was obtained from all patients. RESULTS: A higher proportion of patients achieved sustained remission sooner in the RA cohort than in the SLE cohort, 58% vs. 30.6% of the patients, after 30.8±23.9 vs. 59.4±37.5 months, respectively, p≤0.001. At sustained remission, RA patients scored better than SLE patients in 6 out of 8 domains of the SF-36v2 and the physical health component summary (PHCS); the opposite figure was true for the mental component. Age (ß: 1.06, 95% CI: 1.02-1.1, p=0.03) and SLE diagnosis (ß: 9.64, 95% CI: 3.61-25.75, p≤0.001) were predictors of not achieving normative PHCS. CONCLUSIONS: RA patients in sustained remission achieved better quality of life than SLE patients.

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OBJECTIVE: The aim of this study was to estimate the age at natural menopause in women with SLE. METHODS: One thousand and thirty-nine consecutive SLE patients <60 years of age were surveyed. Demographic and clinical data were queried by a single investigator. SLE characteristics and co-morbidities were retrieved from their medical records. Natural menopause was defined as amenorrhoea ≥12 months in the absence of previous hysterectomy, CYC exposure and severe chronic kidney disease (SCKD). Pregnant women and those with menses during the 12 months prior to interview were considered premenopausal. Median age at menopause was estimated by both logit and survival analyses. In addition, mean age at menopause was calculated for patients aged ≥40 years. Factors associated with age at natural menopause were assessed by Cox regression analysis. RESULTS: A total of 961 SLE women were analysed. At interview, most patients (81.6%) were premenopausal, 7.9% had natural menopause, 6.3% were postmenopausal previously exposed to CYC, 4.1% had undergone hysterectomy before menopause and 0.1% presented with SCKD and amenorrhoea. The mean age at interview was 35.2 years (s.d. 10.1), the mean age at SLE diagnosis was 26.9 years (s.d. 8.6) and the mean duration of disease was 8.2 years (s.d. 7.1). The mean recalled age at menopause was 46.4 years (s.d. 4.7). Median age at menopause estimated by logit and survival analyses were 50.7 and 50.8 years, respectively. Only the age at SLE diagnosis was associated with age at natural menopause. CONCLUSION: Median age at natural menopause in women with lupus is 50 years. This is consistent with the age at menopause reported in the general population.

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OBJECTIVE: To determine the prevalence of SS in a cohort of recent-onset SLE patients and evaluate the clinical and immunological variables that may identify SLE patients prone to develop SS. METHODS: A total of 103 patients participating in a prospective cohort of recent-onset SLE were assessed for fulfilment of the American European Consensus Group criteria for SS using a three-phase approach: screening (European questionnaire, Schirmer-I test and wafer test), confirmation (fluorescein staining test, non-stimulated whole-salivary flow and anti-Ro/La antibodies) and lip biopsy. Anti-Ro/SSA and anti-La/SSB antibodies and RF were measured at entry into the cohort and at SS assessment. RESULTS: Ninety-three females and 10 males were included. Mean age at lupus diagnosis was 25.9 ± 8.9 years, and lupus duration at SS assessment was 30.9 ± 9.1 years. SS was diagnosed in 19 (18.5%) patients, all female, and the patients were older at SLE diagnosis than patients without SS (30.8 ± 9.3 vs 24 ± 8.8 years, P = 0.004). Anti-Ro/SSA antibody was more common in SLE-SS patients (84% vs 55%, P = 0.02, LR + 1.53, 95% CI 1.14, 2.04). In the multivariate analysis, age ≥25 years and anti-Ro/SSA antibodies at SLE diagnosis were identified as predictors of SLE-SS, while the absence of anti-Ro/SSA, anti-La/SSB and RF seems to be protective (LR- 0.14, 95% CI 0.02, 0.95). CONCLUSION: The overlap of SLE and SS occurs in almost one-fifth of SLE patients and presents early during its evolution. SLE onset at age ≥25 years plus the presence of anti-Ro/SSA antibody at diagnosis are useful predictors, while the absence of anti-Ro/SSA, anti-La/SSB and RF identifies patients at lowest risk.

Assuntos