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The plasma bacterial killing ability (BKA) is modulated by the stress response in vertebrates, including amphibians. The complement system is an effector mechanism comprised of a set of proteins present in the plasma that once activated can promote bacterial lysis. Herein, we investigated whether changes in plasma BKA as a result of the acute stress response and an immune challenge are mediated by the complement system in Rhinella diptycha toads. Additionally, we investigated whether the observed changes in plasma BKA are associated with changes in plasma corticosterone levels (CORT). We subjected adult male toads to a restraint or an immune challenge (with three concentrations of Aeromonas hydrophila heat inactivated), and then evaluated the plasma BKA against A. hydrophila, in vitro. We determined the complement system activity on plasma BKA, by treating the plasma (baseline, 1 h and 24 h post-restraint, and after the immune challenge) with ethylenediaminetetraacetic acid, heat, or protease. Our results showed increased CORT 1 h and 24 h after restraint and decreased plasma BKA 24 h post-restraint. The inhibitors of the complement system decreased the plasma BKA compared with untreated plasma at all times (baseline, 1 h, and 24 h after restraint), demonstrating that the plasma BKA activity is partially mediated by the complement system. The immune challenge increased CORT, with the highest values being observed in the highest bacterial concentration, compared with control. The plasma BKA was not affected by the immune challenge but was demonstrated to be partially mediated by the complement system. Our results demonstrated that restraint and the immune challenge activated the hypothalamus-pituitary-interrenal axis, by increasing plasma CORT levels in R. diptycha. Also, our results demonstrated the complement system is participative in the plasma BKA for baseline and post-stress situations in these toads.

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BACKGROUND: Leishmania tarentolae is a non-pathogenic species found in lizards representing an important model for Leishmania biology. However, several aspects of this Sauroleishmania remain unknown to explain its low level of virulence. OBJECTIVES: We reported several aspects of L. tarentolae biology including glycoconjugates, proteolytic activities and metabolome composition in comparison to pathogenic species (Leishmania amazonensis, Leishmania braziliensis, Leishmania infantum and Leishmania major). METHODS: Parasites were cultured for extraction and purification of lipophosphoglycan (LPG), immunofluorescence probing with anti-gp63 and resistance against complement. Parasite extracts were also tested for proteases activity and metabolome composition. FINDINGS: Leishmania tarentolae does not express LPG on its surface. It expresses gp63 at lower levels compared to pathogenic species and, is highly sensitive to complement-mediated lysis. This species also lacks intracellular/extracellular activities of proteolytic enzymes. It has metabolic differences with pathogenic species, exhibiting a lower abundance of metabolites including ABC transporters, biosynthesis of unsaturated fatty acids and steroids, TCA cycle, glycine/serine/threonine metabolism, glyoxylate/dicarboxylate metabolism and pentose-phosphate pathways. MAIN CONCLUSIONS: The non-pathogenic phenotype of L. tarentolae is associated with alterations in several biochemical and molecular features. This reinforces the need of comparative studies between pathogenic and non-pathogenic species to elucidate the molecular mechanisms of virulence during host-parasite interactions.

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Plasmid-encoded toxin (Pet) is an autotransporter protein of the serine protease autotransporters of Enterobacteriaceae (SPATE) family, important in the pathogenicity of Escherichia coli. The pet gene was initially found in the enteroaggregative E. coli (EAEC) virulence plasmid, pAA2. Although this virulence factor was initially described in EAEC, an intestinal E. coli pathotype, pet may also be present in other pathotypes, including extraintestinal pathogenic strains (ExPEC). The complement system is an important defense mechanism of the immune system that can be activated by invading pathogens. Proteases produced by pathogenic bacteria, such as SPATEs, have proteolytic activity and can cleave components of the complement system, promoting bacterial resistance to human serum. Considering these factors, the proteolytic activity of Pet and its role in evading the complement system were investigated. Proteolytic assays were performed by incubating purified components of the complement system with Pet and Pet S260I (a catalytic site mutant) proteins. Pet, but not Pet S260I, could cleave C3, C5 and C9 components, and also inhibited the natural formation of C9 polymers. Furthermore, a dose-dependent inhibition of ZnCl2-induced C9 polymerization in vitro was observed. E. coli DH5α survived incubation with human serum pre-treated with Pet. Therefore, Pet can potentially interfere with the alternative and the terminal pathways of the complement system. In addition, by cleaving C9, Pet may inhibit membrane attack complex (MAC) formation on the bacterial outer membrane. Thus, our data are suggestive of a role of Pet in resistance of E. coli to human serum.

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In arthropods, hematophagy has arisen several times throughout evolution. This specialized feeding behavior offered a highly nutritious diet obtained during blood feeds. On the other hand, blood-sucking arthropods must overcome problems brought on by blood intake and digestion. Host blood complement acts on the bite site and is still active after ingestion, so complement activation is a potential threat to the host's skin feeding environment and to the arthropod gut enterocytes. During evolution, blood-sucking arthropods have selected, either in their saliva or gut, anticomplement molecules that inactivate host blood complement. This review presents an overview of the complement system and discusses the arthropod's salivary and gut anticomplement molecules studied to date, exploring their mechanism of action and other aspects related to the arthropod-host-pathogen interface. The possible therapeutic applications of arthropod's anticomplement molecules are also discussed.

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Post-streptococcal glomerulonephritis is a condition resulting from infection by group A beta-hemolytic streptococcus. The main mechanism involves the formation of immune complexes formed in the circulation or in situ on the glomerular basement membrane, which activates complement and causes various inflammatory processes. Cellular mechanisms have been reported in the induction of kidney damage represented by the infiltration of innate cells (neutrophils and monocyte/macrophages) and adaptive cells (CD4 + lymphocytes and CD8 + lymphocytes) of the immune system. These cells induce kidney damage through various mechanisms. It has been reported that nephritogenic antigens are capable of inducing inflammatory processes early, even before the formation of immune complexes. Usually, this disease progresses towards clinical and renal normalization; however, in a smaller number of patients, it evolves into chronicity and persistent kidney damage. Hypotheses have been proposed regarding the mechanisms underlying this progression to chronicity including failure to induce apoptosis and failure to phagocytose apoptotic cells, allowing these cells to undergo membrane permeabilization and release pro-inflammatory molecules into the environment, thereby perpetuating renal inflammation. Other mechanisms involved include persistent infection, genetic background of the host's complement system, tubulointerstitial changes, and pre-existing kidney damage due to old age and comorbidities.

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Streptococcus sanguinis is a ubiquitous commensal species of the oral cavity commonly involved as an opportunistic pathogen in cardiovascular infections. In this study, we investigated the functions of endopeptidase O (PepO) and a C3-degrading protease (CppA) in the systemic virulence of S. sanguinis. Isogenic mutants of pepO and cppA obtained in strain SK36 showed increased susceptibility to C3b deposition and to opsonophagocytosis by human polymorphonuclear neutrophils (PMN). These mutants differ, however, in their profiles of binding to serum amyloid P component (SAP) and C1q, whereas both showed reduced interaction with C4b-binding protein (C4BP) and/or factor H (FH) regulators as compared to SK36. The two mutants showed defects in ex vivo persistence in human blood, serum-mediated invasion of HCAEC endothelial cells, and virulence in a Galleria mellonella infection model. The transcriptional activities of pepO and cppA, assessed by RT-qPCR in nine wild-type strains, further indicated strain-specific profiles of pepO/cppA expression. Moreover, non-conserved amino acid substitutions were detected among the strains, mostly in CppA. Phylogenetic comparisons with homologues of streptococcal species of the oral and oropharyngeal sites suggested that S. sanguinis PepO and CppA have independent ancestralities. Thus, this study showed that PepO and CppA are complement evasion proteins expressed by S. sanguinis in a strain-specific manner, which are required for multiple functions associated with cardiovascular virulence.

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The systemic increase in inflammatory mediator levels can induce diverse pathological disorders, including potentially thrombus formation, which may be lethal. Among the clinical conditions in which the formation of thrombi dictates the patient's prognosis, envenomation by Bothrops lanceolatus should be emphasized, as it can evolve to stroke, myocardial infarction and pulmonary embolism. Despite their life-threatening potential, the immunopathological events and toxins involved in these reactions remain poorly explored. Therefore, in the present study, we examined the immunopathological events triggered by a PLA2 purified from B. lanceolatus venom, using an ex vivo human blood model of inflammation. Our results showed that the purified PLA2 from the venom of B. lanceolatus damages human erythrocytes in a dose dependent way. The cell injury was associated with a decrease in the levels of CD55 and CD59 complement regulators on the cell surface. Moreover, the generation of anaphylatoxins (C3a and C5a) and the soluble terminal complement complex (sTCC) indicates that human blood exposure to the toxin activates the complement system. Increased production of TNF-α, CXCL8, CCL2 and CCL5 followed complement activation. The venom PLA2 also triggered the generation of lipid mediators, as evidenced by the detected high levels of LTB4, PGE2 and TXB2. The scenario here observed of red blood cell damage, dysfunctions of the complement regulatory proteins, accompanied by an inflammatory mediator storm, suggests that B. lanceolatus venom PLA2 contributes to the thrombotic disorders present in the envenomed individuals.

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The development of new approaches allowing for the early assessment of COVID-19 cases that are likely to become critical and the discovery of new therapeutic targets are urgently required. In this prospective cohort study, we performed proteomic and laboratory profiling of plasma from 163 COVID-19 patients admitted to Bauru State Hospital (Brazil) between 4 May 2020 and 4 July 2020. Plasma samples were collected upon admission for routine laboratory analyses and shotgun quantitative label-free proteomics. Based on the course of the disease, the patients were divided into three groups: (a) mild (n = 76) and (b) severe (n = 56) symptoms, whose patients were discharged without or with admission to an intensive care unit (ICU), respectively, and (c) critical (n = 31), a group consisting of patients who died after admission to an ICU. Based on our data, potential therapies for COVID-19 should target proteins involved in inflammation, the immune response and complement system, and blood coagulation. Other proteins that could potentially be employed in therapies against COVID-19 but that so far have not been associated with the disease are CD5L, VDBP, A1BG, C4BPA, PGLYRP2, SERPINC1, and APOH. Targeting these proteins' pathways might constitute potential new therapies or biomarkers of prognosis of the disease.

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Endometriosis (EM) is a gynecological disorder that presents significant immune dysregulation in its pathophysiology. Recent studies indicate that the Complement System may play a significant role in the immune processes involved in peritoneal clearance and inflammation in EM patients. C5a is a potent anaphylatoxin molecule of complement associated with the development of inflammatory disorders, however its possible impact on EM development requires further investigation. The aim of this study was to determine the concentration of serum C5a in women with EM and to investigate its possible association with severity, symptoms, age and the timing of infertility. Ninety-four patients with EM (from stage I to IV) and 50 healthy controls were assessed for C5a serum levels. Clinical and demographic data were included in the analysis. C5a serum levels were higher in patients with EM than in controls (39.5 ng/mL vs. 26.0 ng/mL; p < .0001), but not different between the EM stages. No association was observed between C5a serum concentration and the presence of symptoms, age, symptom time or infertility time. The C5a serum levels were higher in patients with EM than in controls but not associated with the severity or clinical findings.

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COVID-19 is a complex disease manifesting in a broad severity spectrum and involving distinct organs and systems. Hyperinflammation, including complement over-activation, has a pivotal role in severe COVID-19 pathobiology, stimulating the inflammatory response, causing microangiopathy, platelet-neutrophil activation, and hypercoagulability. SARS-CoV-2 can directly activate the complement system by the classic, alternative, and lectin pathways, and infected cells can produce intracellular complement (the complesome). COVID-19 severity appears to be associated with the degree of complement activation, and it has been hypothesized that patients with COVID-19 may benefit from therapeutic complement inhibition. Different complement cascade molecules may be targeted with potential advantages and disadvantages. Which target(s) is the most effective and when is the best timing for intervention remain open questions. Early phase I and phase II clinical trials have shown promising but conflicting results, warranting phase III controlled randomized trials. Upstream complement inhibition appears to better and more effectively block hyperinflammation with potential clinical significance. Understanding how SARS-CoV-2 exploits the complement system can add precious information about the pathogenesis of other infections, inflammatory, and autoimmune diseases beyond COVID-19.

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Complement factor D (FD) is a rate-limiting enzyme of the alternative pathway (AP). Recent studies have suggested that it is synthesized as an inactive precursor and that its conversion to enzymatically active FD is catalyzed by mannan-binding lectin-associated serine protease 3 (MASP3). However, whether MASP3 is essential for AP complement activity remains uncertain. It has been shown that Masp1/3 gene knockout did not prevent AP complement overactivation in a factor H-knockout mouse, and a human patient lacking MASP3 still retained AP complement activity. In this study, we have assessed AP complement activity in a Masp3-knockout mouse generated by CRISPR/Cas9 editing of the Masp1/3 gene. We confirmed specific Masp3 gene inactivation by showing intact MASP1 protein expression and absence of mature FD in the mutant mice. Using several assays, including LPS- and zymosan-induced C3b deposition and rabbit RBC lysis tests, we detected plasma concentration-dependent AP complement activity in Masp3 gene-inactivated mice. Thus, although not measurable in 5% plasma, significant AP complement activity was detected in 20-50% plasma of Masp3 gene-inactivated mice. Furthermore, whereas FD gene deletion provided more than 90% protection of CD55/Crry-deficient RBCs from AP complement-mediated extravascular hemolysis, Masp3 gene deletion only provided 30% protection in the same study. We also found pro-FD to possess intrinsic catalytic activity, albeit at a much lower level than mature FD. Our data suggest that MASP3 deficiency reduces but does not abrogate AP complement activity and that this is explained by intrinsic pro-FD activity, which can be physiologically relevant in vivo.

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INTRODUCTION: Membranoproliferative glomerulonephritis (MPGN) is a rare glomerular disease with a variable prognosis. A new classification based on the presence or absence of immunoglobulins and complement deposits in immunofluorescence microscopy (IF) of kidney biopsy has recently been proposed. The objectives of the study were to determine and compare the clinical, laboratory, and histopathological characteristics of those with primary or secondary MPGN, reclassify the primary ones based on IF findings, and evaluate kidney outcomes. METHODS: This was an observational retrospective cohort study carried out in a single center (UNIFESP), based on the data collected from medical records of patients followed from 1996 to 2019. RESULTS: Of 53 cases of MPGN, 36 (67.9%) were classified as primary and 17 (32.1%) as secondary MPGN. Most patients were hypertensive (84.9%) and had edema (88.7%) and anemia (84.9%); 33 (91.7%) patients classified as primary MPGN were reclassified as immune-complex-mediated and 3 (8.3%) as complement-mediated. The secondary MPGN group had hematuria more frequently (p <0.001) and a higher prevalence of deposits of IgG (p = 0.02) and C1q (p = 0.003). Regarding the outcome, 39% of the patients achieved partial or complete remission. Lower initial serum albumin and higher initial 24-hour proteinuria were factors associated with worst renal prognosis. CONCLUSIONS: According to the new histological classification, the vast majority of MPGN cases were classified as being mediated by immune complexes. There were few differences between primary and secondary MPGN in relation to their clinical and laboratory characteristics.

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BACKGROUND: Hemolytic uremic syndrome secondary to Shiga-toxin-producing Escherichia coli infection (STEC-HUS) generally shows a favorable outcome. Few cases develop extra-renal complications, since neurological involvement is an important cause of morbidity and mortality. The role of complement in STEC-HUS has been recently highlighted, and the use of eculizumab in severe cases has been communicated. HUS results from environmental and genetic factors, but the simultaneous occurrence of STEC and complement mutations remains undetermined. METHODS: A pediatric case with severe STEC-HUS carrying CFH mutations, with favorable response to eculizumab is analyzed. RESULTS: STEC-HUS was diagnosed in a 4-year-old girl with classic HUS, including low C3. Peritoneal dialysis was started due to hypertension, oligoanuria, and pleural effusion. She evolved with generalized tonic-clonic seizures and required mechanical ventilation. MRI reported multiple supra- and infratentorial ischemic lesions with laminar/striatal cortical necrosis and leukoencephalopathy. After two eculizumab doses, a significative stabilization in diuresis, blood pressure, creatinine, and C3 was achieved. At the third week, episodes of massive digestive bleeding and a life-threatening condition required a colectomy thus preserving the ileocecal valve. Due to atypical evolution, a genetic study was considered, identifying two heterozygous variants (CFH S1191L/V1197A). CONCLUSION: STEC-HUS in patients with a genetic predisposition has been previously reported, but the low frequency of occurrence makes it a rare disease. As in the present case, patients with atypical course might benefit from genetic analysis to evaluate early eculizumab initiation and to better understand its phenotype. A higher resolution version of the Graphical abstract is available as Supplementary information.

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The caterpillar of the Premolis semirufa moth, commonly called Pararama, is found in the Brazilian Amazon region. Contact with the hairs can cause a chronic inflammatory reaction, termed "pararamosis". To date, there is still no specific treatment for pararamosis. In this study, we used a whole human blood model to evaluate the involvement of the complement in the proinflammatory effects of P. semirufa hair extract, as well as the anti-inflammatory potential of complement inhibitors in this process. After treatment of blood samples with the P. semirufa hair extract, there was a significant increase in the generation of soluble terminal complement complex (sTCC) and anaphylatoxins (C3a, C4a, and C5a), as well as the production of the cytokines TNF-α and IL-17 and the chemokines IL-8, RANTES, MIG, MCP-1, and IP-10. The inhibition of C3 with compstatin significantly decreased IL-17, IL-8, RANTES, and MCP-1 production. However, the use of the C5aR1 antagonist PMX205 promoted a reduction in the production of IL-8 and RANTES. Moreover, compstatin decreased CD11b, C5aR1, and TLR2 expression induced by P. semirufa hair extract in granulocytes and CD11b, TLR4, and TLR2 in monocytes. When we incubated vascular endothelial cells with extract-treated human plasma, there was an increase in IL-8 and MCP-1 production, and compstatin was able to decrease the production of these chemokines. C5aR1 antagonism also decreased the production of MCP-1 in endothelial cells. Thus, these results indicate that the extract of the Pararama bristles activates the complement system and that this action contributes to the production of cytokines and chemokines, modulation of the expression of surface markers in leukocytes, and activation of endothelial cells.

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INTRODUCTION: Chagas disease (CD), caused by Trypanosoma cruzi, is a major public health issue worldwide affecting 6-7 million people, mainly in Latin America. The complement system plays a crucial role in host immune defense against T. cruzi infection and during the chronic phase of CD; however, the role of the MBL-associated serine protease 1 (MASP1) gene encoding MASP-1, MASP-3, and MAp44 complement proteins has not yet been reported in CD. This study investigated the possible association between MASP1 gene polymorphisms and MASP-3 protein serum levels in chronic CD and its clinical forms. METHODS: Five polymorphisms of MASP1 gene regulatory regions were genotyped in 214 patients with CD and 197 healthy controls (rs7609662 G>A, rs13064994 C>T, rs72549262 C>G, rs1109452 C>T and rs850314 G>A). MASP-3 serum levels were assessed in 70 patients and 66 healthy controls. Clinical data, serum levels of complement proteins (ficolin-2, ficolin-3 and MBL) and inflammatory markers (pentraxin-3 and hsCRP) were also included in the analyses. RESULTS: A significant association of the MASP1 GC_CCA haplotype with CD (padj= 0.002; OR 3.17 [1.19-8.39]) and chronic chagasic cardiomyopathy (CCC) (padj= 0.013; OR 4.57 [1.37-15.16] was observed. MASP-3 and pentraxin-3 levels were positively correlated in the patients (rho = 0.62; p = 0.0001). MASP-3 levels were not associated with MASP1 polymorphisms or CD and its clinical forms. Furthermore, no correlation was observed between MASP-3 levels and that of ficolin-2, ficolin-3, MBL and hsCRP. CONCLUSION: Our findings suggest a possible role for the MASP1 GC_CCA haplotype in susceptibility to chronic CD and CCC clinical forms.

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The inflammatory component of diabetic kidney disease has become of great interest in recent years, with genetic and epigenetic variants playing a fundamental role in the initiation and progression of the disease. Cells of the innate immune system play a major role in the pathogenesis of diabetic kidney disease, with a lesser contribution from the adaptive immune cells. Other components such as the complement system also play a role, as well as specific cytokines and chemokines. The inflammatory component of diabetic kidney disease is of great interest and is an active research field, with the hope to find potential innovative therapeutic targets.

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Abstract Preeclampsia, a human pregnancy syndrome, is characterized by elevated blood pressure and proteinuria after the 20th week of gestation. Its etiology remains unknown, and its pathophysiological mechanisms are related to placental hypoperfusion, endothelial dysfunction, inflammation, and coagulation cascade activation. Recently, the role of the complement system has been considered. This syndrome is one of the main causes of maternal and fetal mortality and morbidity. This article discusses the hypothesis of preeclampsia being triggered by the occurrence of inadequate implantation of the syncytiotrophoblast, associated with bleeding during the first stage of pregnancy and with augmented thrombin generation. Thrombin activates platelets, increasing the release of antiangiogenic factors and activating the complement system, inducing the membrane attack complex (C5b9). Immature platelet fraction and thrombin generation may be possible blood biomarkers to help the early diagnosis of preeclampsia.

Resumo A pré-eclâmpsia, uma síndrome da gestação humana, é caracterizada por elevação da pressão arterial e proteinúria patológica após a 20ª semana de gestação. Sua etiologia permanece desconhecida, e seus mecanismos fisiopatológicos estão relacionados à hipoperfusão placentária, disfunção endotelial, inflamação, e ativação da cascata de coagulação. Recentemente, o papel do sistema do complemento foi considerado. Essa síndrome é uma das principais causas de morbidade e mortalidade materna e fetal. Este artigo discute a hipótese de a pré-eclâmpsia ser desencadeada pela ocorrência da implantação inadequada do sinciciotrofoblasto, associada ao sangramento durante o primeiro trimestre da gravidez com aumento da geração de trombina. A trombina ativa plaquetas, aumentando a liberação de fatores antiangiogênicos na circulação e ativando o sistema do complemento, especialmente o complexo de ataque de membrana (C5b9). Portanto, a fração de plaquetas imaturas e a geração de trombina podem ser possíveis biomarcadores sanguíneos para auxílio no diagnóstico precoce da pré-eclâmpsia.

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CONTEXT: Global studies on Argemone mexicana L. (Papaveraceae) traditionally used against malaria in Mali are limited to its low-mass compounds activities, and little information on its bioactive polysaccharides is available. OBJECTIVE: This study determines the structure and the immunomodulatory activity of polysaccharides from aerial parts of A. mexicana. MATERIALS AND METHODS: Acidic polysaccharides from this plant material named HMAmA1 and HMAmA2 were isolated from water extracts. Their monosaccharide composition was determined by gas chromatography. Glycosidic linkages were determined using GC-MS. NMR was also applied. The polymers were tested for effects on the human complement system in vitro at different doses. RESULTS: The monosaccharide composition showed that the two polysaccharides contained in different amounts the following monomers: arabinose, rhamnose, galactose, and galacturonic acid. Overall structural analysis showed the presence of a low ratio of 1,2-linked rhamnose compared to 1,4-linked galacturonic acid with arabinogalactans substituted on position 4 of rhamnose. NMR data showed the presence of galacturonans alternated by rhamnogalacturonans bearing arabinose and galactose units. α-Linkages were found for l-arabinose, l-rhamnose and d-galacturonic acid, while ß-linkages were found for d-galactose. The two polysaccharides exhibited strong complement fixation activities, with HMAmA1 being the highest potent fraction. ICH50 value of HMAmA1 was 5 µg/mL, compared to the control BPII being 15.9 µg/mL. DISCUSSION AND CONCLUSIONS: Polysaccharides form A. mexicana presented a complement fixation effect. The complement system is an important part of the immune defense, and compounds acting on the cascade are of interest. Therefore, these polymers may be useful as immunodulatory agents.

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Complement regulatory proteins (mCRPs) CD55, CD46 and CD59 have been proposed as key elements in therapeutic resistance against cancer. mCRP-expressing tumor cells, in addition to hindering trastuzumab, pertuzumab and sacituzumab-govitecan therapeutic activity in breast cancer, can regulate biological processes that promote tumor progression. This review describes the structure of mCRPs and analyzes their expression using transcriptomic databases from breast cancer patients, in addition to collecting information on mCRPs interactions and signaling in tumor cells. Given that mCRPs are relevant targets, several strategies that have been explored for their inhibition and regulation in order to increase therapeutic efficacy and prevent cancer resistance and progression are described.

Se ha propuesto a las proteínas reguladoras de complemento (mCRP) CD55, CD46 y CD59 como piezas clave en la resistencia terapéutica contra el cáncer. Las células tumorales que expresan las mCRP, además de obstaculizar la actividad terapéutica de trastuzumab, pertuzumab y sacituzumab-govitecan en cáncer de mama, pueden regular procesos biológicos que promueven la progresión tumoral. Esta revisión describe la estructura de las mCRP y analiza su expresión a partir de bases de datos transcriptómicos de pacientes con cáncer de mama; también recopila información de interacciones y señalización de las mCRP en células tumorales. Dado que estas mCRP son dianas relevantes, se describen diversas estrategias para su inhibición y regulación para incrementar la eficacia terapéutica y evitar la resistencia y progresión del cáncer.

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