Auto-Immunity Highlights最新文献

Objective: To aid in the selection of the most suitable therapeutic option in patients with diagnosis of rheumatoid arthritis according to the phase of disease, through the review of articles that identify omics biological markers.

Methods: A systematic review in PubMed/Medline databases was performed. We searched articles from August 2014 to September 2019, in English and Spanish, filtered by title and full text; and using the terms "Biomarkers" AND "Rheumatoid arthritis".

Results: This article supplies an exhaustive review from research of objective measurement, omics biomarkers and how disease activity appraise decrease unpredictability in treatment determinations, and finally, economic, and clinical outcomes of treatment options by biomarkers' potential influence. A total of 122 articles were included. Only 92 met the established criteria for review purposes and 17 relevant references about the topic were included as well. Therefore, it was possible to identify 196 potential clinical biomarkers: 22 non-omics, 20 epigenomics, 33 genomics, 21 transcriptomics, 78 proteomics, 4 glycomics, 1 lipidomics and 17 metabolomics.

Conclusion: A biomarker is a measurable indicator of some, biochemical, physiological, or morphological condition; evaluable at a molecular, biochemical, or cellular level. Biomarkers work as indicators of physiological or pathological processes, or as a result of a therapeutic management. In the last five years, new biomarkers have been identified, especially the omics, which are those that proceed from the investigation of genes (genomics), metabolites (metabolomics), and proteins (proteomics). These biomarkers contribute to the physician choosing the best therapeutic option in patients with rheumatoid arthritis.

Background: Rheumatoid arthritis (RA) is a systemic autoimmune disease. The combination therapy of methotrexate (MTX) and Janus kinase inhibitor (JAKi) is commonly used. Patients with RA are at increased risk of malignancy, however, it remains unclear whether the combination therapy is associated with a higher risk.

Objective: To assess the malignancy risk among patients with RA receiving combination therapy of JAKi and MTX compared to MTX alone.

Methods: PubMed, Cochrane and Embase were thoroughly searched for randomized controlled trials (RCTs) in patients with RA receiving JAKi and MTX, from inception to July 2020. Primary endpoints were malignancy events, Non melanomatous skin cancer (NMSC) and malignancy excluding NMSC and secondary endpoints were serious adverse events (SAE), deaths. Risk ratio (RR) and 95% CI were calculated using the Mantel-Haenszel random-effect method.

Results: 659 publications were screened and 13 RCTs with a total of 6911 patients were included in the analysis. There was no statistically significant difference in malignancy [RR = 1.42; 95% CI (0.59, 3.41)], neither NMSC [RR = 1.44 (0.36, 5.76)] nor malignancies excluding NMSC [RR = 1.12 (0.40, 3.13)]. No statistically significant difference between the two groups for SAE [RR = 1.15 (0.90, 1.47)] and deaths [RR = 1.99 (0.75, 5.27)] was found.

Conclusion: The adjunction of JAKi to MTX is not associated with an increased risk of malignancy when compared to MTX alone. There is no increased risk of SAE and deaths when compared to MTX alone in patients with RA.

Background: Multiple Sclerosis (MS) is an autoimmune-mediated disease of the central nervous system. Experimental data suggest a role of intestinal microbiota and microbial products such as short-chain fatty acids (SCFAs) in the pathogenesis of MS. A recent clinical study reported beneficial effects (mediated by immunomodulatory mechanisms) after oral administration of the SCFA propionate in MS patients. Based on available evidence, we investigated whether SCFAs and the fecal inflammation marker calprotectin are altered in MS.

Methods: 76 subjects (41 patients with relapsing-remitting MS and 35 age-matched controls) were investigated in this case-control study. All subjects underwent clinical assessment with established clinical scales and provided fecal samples for a quantitative analysis of fecal SCFA and fecal calprotectin concentrations. Fecal markers were compared between MS patients and controls, and were analyzed for an association with demographic as well as clinical parameters.

Results: Median fecal calprotectin concentrations were within normal range in both groups without any group-specific differences. Fecal SCFA concentrations showed a non-significant reduction in MS patients compared to healthy subjects. Female subjects showed significantly reduced SCFA concentrations compared to male subjects.

Conclusions: In our cohort of MS patients, we found no evidence of an active intestinal inflammation. Yet, the vast majority of the investigated MS patients was under immunotherapy which might have affected the outcome measures. The sex-associated difference in fecal SCFA concentrations might at least partially explain female predominance in MS. Large-scale longitudinal studies including drug-naïve MS patients are required to determine the role of SCFAs in MS and to distinguish between disease-immanent effects and those caused by the therapeutic regime.

Background: Type 1 diabetes (T1D) is an autoimmune disease characterized by the progressive destruction of pancreatic beta cells. Interferon-α (IFNα), an antiviral cytokine, is expressed in the pancreatic islets in early T1D, which may be secondary to viral infections. However, not all patients harboring a type I IFN signature present signals of viral infection, suggesting that this response might be initiated by other "danger signals". Accumulation of mitochondrial double-stranded RNA (mtdsRNA; a danger signal), secondary to silencing of members of the mitochondrial degradosome, PNPT1 and SUV3, has been described to activate the innate immune response.

Methods: To evaluate whether mtdsRNA represents a "danger signal" for pancreatic beta cells in the context of T1D, we silenced PNPT1 and/or SUV3 in slowly proliferating human insulin-secreting EndoC-βH1 cells and in non-proliferating primary human beta cells and evaluated dsRNA accumulation by immunofluorescence and the type I IFN response by western blotting and RT-qPCR.

Results: Only the simultaneous silencing of PNPT1/SUV3 induced dsRNA accumulation in EndoC-βH1 cells but not in dispersed human islets, and there was no induction of a type I IFN response. By contrast, silencing of these two genes individually was enough to induce dsRNA accumulation in fibroblasts present in the human islet preparations.

Conclusions: These data suggest that accumulation of endogenous mtdsRNA following degradosome knockdown depends on the proliferative capacity of the cells and is not a mediator of the type I IFN response in human pancreatic beta cells.

Background: Granulomatosis with polyangiitis (GPA) is a systemic autoimmune disease characterized by small and medium vessel vasculitis. The use of biological therapies such as rituximab and infliximab has improved the treatment of ocular manifestations in GPA.

Case report: We report a case of a 45-year-old Caucasian male suffering with rhinitis, sinubronchitis and exophthalmos. These clinical findings, subsequent biopsy and MRI were consistent with positive anti-neutrophil cytoplasm antibody (ANCA)/proteinase-3 and he was diagnosed with GPA with orbital involvement. He was refractory to cyclophosphamide at stable doses of methotrexate and a therapy with rituximab was started. Eventually and because of family planning methotrexate was replaced by azathioprine. Symptoms worsened and MRI revealed an increase in the granulomatous lesion in the orbit. Therefore, we decided to add infliximab to the combination of azathioprine and rituximab, our patient achieved then a long-term response. During the 10 years of the combined treatment, no adverse effects or systemic involvement occurred.

Conclusions: This case suggests that the individual use of a combination of rituximab and infliximab may be a promising strategy for the treatment in the long term of refractory orbital GPA.

Background: To evaluate the interpretation and reporting of antinuclear antibodies (ANA) by indirect immunofluorescence assay (IFA) using HEp-2 substrates based on common practice and guidance by the International Consensus on ANA patterns (ICAP).

Method: Participants included two groups [16 clinical laboratories (CL) and 8 in vitro diagnostic manufacturers (IVD)] recruited via an email sent to the Association of Medical Laboratory Immunologists (AMLI) membership. Twelve (n = 12) pre-qualified specimens were distributed to participants for testing, interpretation and reporting HEp-2 IFA. Results obtained were analyzed for accuracy with the intended and consensus response for three main categorical patterns (nuclear, cytoplasmic and mitotic), common patterns and ICAP report nomenclatures. The distributions of antibody titers of specimens were also compared.

Results: Laboratories differed in the categorical patterns reported; 8 reporting all patterns, 3 reporting only nuclear patterns and 5 reporting nuclear patterns with various combinations of other patterns. For all participants, accuracy with the intended response for the categorical nuclear pattern was excellent at 99% [95% confidence interval (CI): 97-100%] compared to 78% [95% CI 67-88%] for the cytoplasmic, and 93% [95% CI 86%-100%] for mitotic patterns. The accuracy was 13% greater for the common nomenclature [87%, 95% CI 82-90%] compared to the ICAP nomenclature [74%, 95% CI 68-79%] for all participants. Participants reporting all three main categories demonstrated better performances compared to those reporting 2 or less categorical patterns. The average accuracies varied between participant groups, however, with the lowest and most variable performances for cytoplasmic pattern specimens. The reported titers for all specimens varied, with the least variability for nuclear patterns and most titer variability associated with cytoplasmic patterns.

Conclusions: Our study demonstrated significant accuracy for all participants in identifying the categorical nuclear staining as well as traditional pattern assignments for nuclear patterns. However, there was less consistency in reporting cytoplasmic and mitotic patterns, with implications for assigning competencies and training for clinical laboratory personnel.

Swelling and the progressive destruction of articular cartilage are major characteristics of rheumatoid arthritis (RA), a systemic autoimmune disease that directly affects the synovial joints and often causes severe disability in the affected positions. Recent studies have shown that type B synoviocytes, which are also called fibroblast-like synoviocytes (FLSs), as the most commonly and chiefly resident cells, play a crucial role in early-onset and disease progression by producing various mediators. During the pathogenesis of RA, the FLSs' phenotype is altered, and represent invasive behavior similar to that observed in tumor conditions. Modified and stressful microenvironment by FLSs leads to the recruitment of other immune cells and, eventually, pannus formation. The origins of this cancerous phenotype stem fundamentally from the significant metabolic changes in glucose, lipids, and oxygen metabolism pathways. Moreover, the genetic abnormalities and epigenetic alterations have recently been implicated in cancer-like behaviors of RA FLSs. In this review, we will focus on the mechanisms underlying the transformation of FLSs to a cancer-like phenotype during RA. A comprehensive understanding of these mechanisms may lead to devising more effective and targeted treatment strategies.

Background: Systemic lupus erythematosus (SLE) is a clinicopathologically heterogeneous chronic autoimmune disorder affecting different organs and tissues. It has been reported that there is an increasing rate of SLE incidence among Iranian population. Moreover, the Iranian SLE patients have more severe clinical manifestations compared with other countries. Therefore, it is required to introduce novel methods for the early detection of SLE in this population. Various environmental and genetic factors are involved in SLE progression.

Main body: In present review we have summarized all of the reported genes which have been associated with clinicopathological features of SLE among Iranian patients.

Conclusions: Apart from the reported cytokines and chemokines, it was interestingly observed that the apoptosis related genes and non-coding RNAs were the most reported genetic abnormalities associated with SLE progression among Iranians. This review clarifies the genetics and molecular biology of SLE progression among Iranian cases. Moreover, this review paves the way of introducing an efficient panel of genetic markers for the early detection and better management of SLE in this population.

Background: Microscopic polyangiitis (MPA) is a subtype of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV), involving small and medium sized vessels, often affecting the kidneys and lungs. Anti-neutrophil cytoplasmic antibody (ANCA) is detected in up to 90% of cases of MPA and its detection helps guide diagnosis, however cases of ANCA-negative MPA have been reported, hence definitive diagnosis relies on tissue biopsy.

Case report: A 23-year-old man was evaluated for dyspnea and pleuritic chest pain, and found to have bilateral intra-alveolar opacities and hilar adenopathy. Diagnostic work up revealed positive anti-nuclear antibodies (ANA) and negative ANCA, which in the setting of a non-classical presentation, delayed diagnosis and appropriate treatment. Due to persistent symptoms and a high suspicion for autoimmune disease with pulmonary-renal syndrome, he underwent lung biopsy which revealed intra-alveolar hemorrhage and capillaritis indicative of microscopic polyangiitis (MPA). Surprisingly, kidney biopsy was not typical of classic MPA, but revealed less common features. Due to therapeutic noncompliance he was readmitted multiple times thereafter with rare complications of MPA such as acute pancreatitis and hemorrhagic pericardial effusion with tamponade.

Conclusion: This case serves as an important clinical reminder to consider AAV even in those with negative ANCA serologies and a high suspicion for pulmonary-renal syndrome. It also demonstrates the high morbidity in cases of diagnostic delay and inadequate treatment.

Background: The soluble form of CTLA-4 (sCTLA-4) is associated with several autoimmune diseases. The aim of the study is to measure the serum sCTLA-4 levels in type I diabetic (T1DM) patients and to assess the presence of autoantibodies for a possible association.

Methods: One hundred forty-two T1DM patients were enrolled in the study. Fifty of them were serologically positive for co-existing autoantibodies. One hundred and five subjects were enrolled in the study, as non-diabetic controls (1-17 years of age; median age-10 years). The serum samples of all the subjects were analyzed with ELISA to detect the concentration of sCTLA-4 and anti-GAD/IA2 IgG. Standard statistical analysis was conducted as required.

Results: Ninety-four (66%) subjects of T1DM patients and five (4.7%) subjects of the non-diabetic group had antibodies positive for anti-GAD/IA2. Serum sCTLA-4 was low in most of the subjects of both the diabetic and control groups (p = 0.18). In the control group, nine individuals (8.6%) were positive for sCTLA-4. Similarly, only seven patients (4.9%) in the T1DM group had high levels of sCTLA-4, of which two were found to be double positive for anti-thyroid peroxidase and anti-thyroglobulin antibodies. In addition, among the T1DM patients, no significant relationships were observed between sCTLA-4 levels and age of onset (p = 0.43), disease duration (p = 0.09), or glycemic control (p = 0.32).

Conclusion: Despite the previous findings of high sCTLA-4 levels in autoimmune diseases, serum levels of sCTLA-4 are not significantly different between T1DM patients and non-diabetic adolescents. Furthermore, we did not observe any association with autoantibody presence, glycemic control, or disease duration.