CD32 (FcγRIIB) expression is low on CD21low B cells from systemic sclerosis patients with digital ulcers, interstitial lung disease, and anti-topoisomerase I autoantibodies.

CD21low B cells have recently been found increased in SSc-associated digital ulcers (DUs) or interstitial lung disease (ILD). To further characterize CD21low B cells which encompass autoreactive cells, we analyzed their expression of the inhibitory CD32 receptor in SSc. Peripheral blood mononuclear cells from 27 patients with SSc and 15 age-and sex-matched healthy controls (HCs) were analyzed with multicolor flow cytometry. CD21low B cells were significantly increased in patients with DUs (51.3%) compared to HCs (28.1%) and in patients with ILD (53.1%) compared to HCs. CD21lowCD32low B cells were significantly increased in patients with DUs (23.8%) compared to HCs (4.4%), in patients with ILD (28.4%) compared to HCs, and in anti-topoisomerase I (+) patients (21.5%) compared to HCs and to anti-topoisomerase I (-) patients (2.4%). Autoreactive B cells recognizing Topoisomerase I were predominantly within CD32low cell fraction. Our study further supports the autoreactive status of CD21lowCD32low B cells in SSc patients.

Sex bias in immune response: it is time to include the sex variable in studies of autoimmune rheumatic diseases.

Healthy females and males differ in their immune cell composition and function and females generally mount stronger immune response than males and are much more susceptible to autoimmune rheumatic diseases. Females differ from males in sex hormones, and X-chromosome genes. Sex hormones affect immune cells and responses, and may induce epigenetic DNA changes. The importance of X-chromosome genes is exemplified in men with the Klinefelter syndrome (47,XXY) who have an additional X-chromosome and develop systemic lupus erythematosus(SLE) as frequently as women. X-chromosome contains genes critical for the immune response, such as FOXP3, toll-like receptor(TLR)7, TLR8, CD40 Ligand, IL2RG, IL9R, BTK, and others. Whereas one X-chromosome in females is randomly inactivated early in embryonic development, around 25% of X-linked genes escape inactivation and result in more X-linked gene dosage in females. We use two key female-biased autoimmune rheumatic diseases, SLE and systemic sclerosis, to review differences in immune response, and clinical manifestations between females and males. The inclusion of sex variable in research will facilitate precision medicine and optimal patient outcome.

Emotional intelligence: a novel predictor of quality of life in patients with systemic sclerosis.

Systemic sclerosis (SSc), a chronic systemic autoimmune disease, affects skin and internal organs compromising organ function and leading to significant morbidity and poor health-related quality of life (HrQoL). This cross-sectional study investigated whether HrQoL is influenced by trait emotional intelligence (TEI). Sixty patients with SSc (Female: 86.67%) completed the socio-demographic characteristics form, TEI Questionnaire Short-Form (TEIQue-SF), and Short-Form Health Survey (SF-36). Sixty healthy controls were also completed the TEIQue-SF. A series of multiple linear regression analyses with correlation matrix was used to analyze SF-36 domains as dependent variables with TEI domains (well-being, self-control, emotionality, sociability) as independent variables. The average age of participants was 57.3 ± 12.9 years with a mean disease duration of 7.7 ± 6.7 years. Patients differed from controls in the sociability domain of TEI. TEI global was found to affect the physical and mental component summaries (p < .001), and all 8 dimensions of the HrQoL (p < .001). Age, disease duration, and gastrointestinal manifestations were negatively associated with various components of SF-36. TEI was positively associated with all dimensions of HrQoL. Understanding the relationship between TEI and HrQoL dimensions is important for the support and empowerment of SSc patients, as well as the establishment and implementation of appropriate psychotherapeutic interventions.

The role of B cells in the pathogenesis of systemic sclerosis: an update.

The pathogenesis of SSc is incompletely understood, but several lines of evidence suggest that B cells are involved. Effector B (Beff) cells are hyperactivated and produce autoantibodies (autoAbs), and regulatory B cells (Bregs) are decreased, although a recent study reported a defect in central B cell tolerance. AutoAbs appear before fibrosis, and some have direct profibrotic effects, while others also induce microvasculopathy. Recently, a study found that B cells reactive to topo I with high affinity produce IL-6 and cause fibrosis in mice, whereas B cells with low affinity for topo I produce IL-10 and inhibit fibrosis. Ibrutinib, a Bruton's tyrosine kinase inhibitor, promoted B cells with low affinity for topo I and decreased fibrosis. These findings provide a rationale for innovative B cell-directed strategies for managing SSc, such as ibrutinib or chimeric antigen receptor T cells, particularly in the early inflammatory stage of the disease.

Efficacy of n-3 fatty acid supplementation on rheumatoid arthritis' disease activity indicators: a systematic review and meta-analysis of randomized placebo-controlled trials.

Theoretical evidence and previous studies suggest that oralnutrient supplementation (ONS) with n-3 fatty acids for rheumatoid arthritis (RA) has the potential to lower disease activity indicators and non-steroidal anti-inflammatory drug (NSAID) uptake. A systematic search was conducted on five databases/registries from inception until May 23, 2021 with the aim to identify randomized placebo-controlled trials comparing n-3 supplements to placebo on disease-specific outcomes. A total of 23 studies matched the criteria (PROSPERO: CRD42019137041). Pooled analyses revealed that n-3 ONS provided a small effect in reducing pain [standardized mean difference (SMD): -0.16, 95% confidence intervals (CI): -0.40 to 0.09], and tender (SMD: -0.20, 95% CI: -0.46 to 0.05) and swollen joint count (SMD: -0.10, 95% CI: -0.28 to 0.07). In sensitivity analyses, there was a small effect in the reduction of NSAIDs intake (SMD: -0.22, 95% CI: -0.90 to 0.46), and c-reactive protein was reduced only by 0.21 mg/dL (95% CI: -0.75 to 0.33). Similar findings were observed regarding other objective/subjective outcomes. The certainty of the evidence was mostly of "very low/low" quality. Overall, n-3 ONS in RA might have a limited clinical benefit. Previous findings suggesting a reduction in NSAID intake may have been biased from the inadequate blinding of interventions.

Incidence, risk factors and validation of the RABBIT score for serious infections in a cohort of 1557 patients with rheumatoid arthritis.

OBJECTIVES: Predicting serious infections (SI) in patients with rheumatoid arthritis (RA) is crucial for the implementation of appropriate preventive measures. Here we aimed to identify risk factors for SI and to validate the RA Observation of Biologic Therapy (RABBIT) risk score in real-life settings. METHODS: A multi-centre, prospective, RA cohort study in Greece. Demographics, disease characteristics, treatments and comorbidities were documented at first evaluation and one year later. The incidence of SI was recorded and compared with the expected SI rate using the RABBIT risk score. RESULTS: A total of 1557 RA patients were included. During follow-up, 38 SI were recorded [incidence rate ratio (IRR): 2.3/100 patient-years]. Patients who developed SI had longer disease duration, higher HAQ at first evaluation and were more likely to have a history of previous SI, chronic lung disease, cardiovascular disease and chronic kidney disease. By multivariate analysis, longer disease duration (IRR: 1.05; 95% CI: 1.005, 1.1), history of previous SI (IRR: 4.15; 95% CI: 1.7, 10.1), diabetes (IRR: 2.55; 95% CI: 1.06, 6.14), chronic lung disease (IRR: 3.14; 95% CI: 1.35, 7.27) and daily prednisolone dose ≥10 mg (IRR: 4.77; 95% CI: 1.47, 15.5) were independent risk factors for SI. Using the RABBIT risk score in 1359 patients, the expected SI incidence rate was 1.71/100 patient-years, not different from the observed (1.91/100 patient-years; P = 0.97). CONCLUSION: In this large real-life, prospective study of RA patients, the incidence of SI was 2.3/100 patient-years. Longer disease duration, history of previous SI, comorbidities and high glucocorticoid dose were independently associated with SI. The RABBIT score accurately predicted SI in our cohort.

Major vault protein/lung resistance related protein: a novel biomarker for rheumatoid arthritis.

OBJECTIVES: Rheumatoid arthritis (RA) can lead to joint destruction and early institution of effective treatment can preserve joint function. Biomarkers can establish early diagnosis and predict effect of treatment. Vault particles, large cytoplasmic ribonucleoprotein particles that participate in inflammation, might serve as biomarkers. The aim of this study was to assess the diagnostic and the prognostic value of major vault protein (MVP) and their antibodies in RA. METHODS: Serum samples from 159 RA patients, 26 early RA (ERA) patients, 21 patients with osteoarthritis (OA) and 30 healthy individuals were tested for MVP, anti-cyclic citrullinated peptide (anti-CCP) and C-reactive protein (CRP) using enzyme-linked immunosorbent assays (ELISA). Rheumatoid factor (RF) was tested by nephelometry, and anti-MVP antibodies were detected by anti-MVP peptide ELISA using an in-house protocol. RESULTS: MVP levels were higher in RA and ERA, compared to OA and healthy controls (p<0.00001). A combination of MVP with RF or anti-CCP showed an improved diagnostic accuracy compared to RF or anti-CCP alone in RA and ERA. MVP exhibited similar AUC levels to anti-CCP and RF in RA whereas in ERA, MVP exhibited the same or slightly higher AUC levels, compared to anti-CCP and RF, respectively. High MVP levels were associated with lack of response to treatment. Levels of anti-MVP peptide 2 antibodies were significantly higher in RA compared to healthy controls (t= 2.73, p=0.007). CONCLUSIONS: MVP and autoantibodies against MVP may have the potential to serve as diagnostic and prognostic biomarkers in RA.

Immune checkpoint inhibitor-induced musculoskeletal manifestations.

Immune checkpoint inhibitors (ICI) associate with a wide range of immune-related adverse events (Ir-AE), including musculoskeletal manifestations. We aimed at identifying all studies reporting musculoskeletal Ir-AE. An electronic (Medline, Scopus and Web of Science) search was performed using two sets of key words. The first set consisted of: arthritis, musculoskeletal, polymyalgia rheumatica and myositis. The second set consisted of: anti-PD-1, anti-PD-L1, anti-CTLA-4, ipilimumab, tremelimumab, pembrolizumab, nivolumab, atezolizumab, avelumab and durvalumab. We identified 3 prospective studies, 17 retrospective studies and 4 case series reporting 363 patients in total. Combined data from all three prospective studies provide a prevalence rate of 6.13%. Most patients were males (59.68%) and the vast majority (73%) were on programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitors. Most studies report a median time of ≤ 12 weeks from first ICI administration to symptom onset. The main clinical phenotypes reported were: (a) inflammatory arthritis (57.57%), (b) myositis (14.04%) and (c) polymyalgia rheumatica (PMR) (12.12%). A total of 256 patients required steroids (70.52%) and 67 patients (18.45%) were treated with DMARDs. Positive auto-antibodies and family history of any autoimmune disease were present in 18.48% and 19.04% of cases, respectively. Only a few patients (19%) had to discontinue treatment due to musculoskeletal Ir-AE. Two prospective studies show that significantly more patients with musculoskeletal Ir-AE exhibit a favorable oncologic response compared to patients not exhibiting such manifestations whereas retrospective studies show that 77.22% of patients with musculoskeletal Ir-AE have a good tumor response. One out of 15 patients treated with ICI will develop musculoskeletal Ir-AE; in most cases the severity of these manifestations is mild/moderate and usually ICI may be continued. Rheumatologists should familiarize with this new clinical entity and develop relevant therapeutic algorithms.

Adrenocorticotropic hormone: an effective "natural" biologic therapy for acute gout?

Treatment of acute gout consists of non-steroidal anti-inflammatory drugs (NSAIDs), colchicine and steroids. However, the typical patient with gout has multiple comorbidities such as cardiovascular disease, hypertension, renal dysfunction or diabetes/metabolic syndrome that represent contraindications to these therapeutic options. The aim of this study is to review the available evidence regarding the use of ACTH as an alternative therapeutic option for acute gout and explore potential mechanisms of action. We performed an electronic search (MEDLINE, Scopus and Web of Science) using the keywords ACTH or adrenocorticotropic hormone combined with gout or crystal-induced arthritis. ACTH appears suitable for patients with many comorbidities due to its good safety profile. Clinical evidence shows that ACTH is at least as effective as classic agents. The mechanism of action of ACTH in gout is not entirely known. Robust experimental evidence points to the direction that ACTH does not act solely by triggering the release of endogenous steroids but also appears to downregulate inflammatory responses by activating melanocortin receptors on innate immune cells, such as macrophages. Moreover, indirect evidence indicates that ACTH may have an IL-1 antagonistic effect. We propose that ACTH may be an alternative therapeutic option for gout in patients with multiple comorbidities. Large-scale studies assessing the efficacy and safety of ACTH compared to classic therapeutic options are needed.

A study of antigen-specific anti-cytomegalovirus antibody reactivity in patients with systemic sclerosis and concomitant anti-Ro52 antibodies.

Anti-Ro52 autoantibody (autoAb), highly prevalent in Sjogren's syndrome (SjS) and systemic lupus erythematosus (SLE), is also frequent in systemic sclerosis (SSc). Viral agents, such as human cytomegalovirus (HCMV), have been considered as a trigger for SSc and SSc-associated autoAbs. To seek for antigen-specific anti-HCMV associations with anti-Ro52, we assessed the dominant anti-HCMV ab responses in anti-Ro52 antibody (ab)-positive and -negative patients with SSc and compared them with those in SLE and SjS. 116 Anti-HCMV ab(+) sera were analyzed, including 70 from anti-Ro52(+) patients (29 SSc, 23 SLE and 18 SjS) and 46 from anti-Ro52(-) patients (29 with SSc, 9 with SLE and 8 with SjS) as negative controls. Abs against specific HCMV pp130/UL57, pp65/UL83, pp55/UL55, pp52/UL44, p38 and pp28/UL99 antigens were tested by immunoblotting. Anti-Ro52(+) SSc patients reacted more frequently against pp52/UL44 and p38 compared to anti-Ro52(-) [(13/29, 44.8%; 95% CI 26.7-62.9% vs. 1/29, 3.4%; 95% CI 0-10%, p < 0.001, and 9/29, 31.0%; 95% CI 14.2-47.8% vs. 2/29, 6.9%; 95% CI 0-16.1%, p = 0.041, respectively]. No such differences were noted between anti-Ro52(+) and anti-Ro52(-) SLE or SjS patients. Also, antibody titres against HCMV pp65/UL83, pp52/UL44 and p38 antigens were higher in anti-Ro52(+) than anti-Ro52(-) SSc patients (p < 0.01). Ab responses against specific HCMV antigens differ among anti-Ro52 ab-positive and -negative patients with SSc (as well as between SSc and SLE or SjS), but whether these differences are epiphenomenal remains to be seen.

A comprehensive analysis of antigen-specific antibody responses against human cytomegalovirus in patients with systemic sclerosis.

Anti-human cytomegalovirus (HCMV) antibodies are considered triggers of systemic sclerosis (SSc), but such a hypothesis has been assessed in limited sub-dominant epitopes. Our aim was to systematically assess the potential association of HCMV antibodies targeting most immunodominant and subdominant viral antigens, as this would reveal immunopathogenic associations. Our study included 110 SSc patients, 60 multiple sclerosis (MS) patients, and 51 healthy controls (HC). Anti-HCMV abs were tested by immunoblotting. IgG anti-HCMV was broader in SSc and MS compared to HC. Anti- UL57 and UL55 were more frequent in SSc versus MS forms. Reactivity to multiple viral antigens was more frequent in SSc than MS forms. Anti-viral antibodies levels were higher in specific autoantibody-positive SSc patients compared to seronegative cases. In conclusion, more prevalent and/or stronger antigen-specific HCMV responses are noted in SSc compared to controls, implying a role of these viral responses in SSc development.

Apremilast increases IL-10-producing regulatory B cells and decreases proinflammatory T cells and innate cells in psoriatic arthritis and psoriasis.

OBJECTIVES: Psoriatic arthritis (PsA) and psoriasis are immune-mediated inflammatory diseases sharing common immunological mechanisms. Regulatory B cells (Breg cells) producing IL-10 (B10 cells), a critical anti-inflammatory B-cell subset, were found to be decreased in both PsA and psoriasis. Apremilast, a phosphodiesterase-4(PDE4) inhibitor, increases IL-10 and therefore, we examined the effect of apremilast on Breg cells. METHODS: Fifty patients, including 20 with PsA and 30 with psoriasis, were included in the study. The effect of apremilast on Breg cells at 3, 6 and 12 months post-treatment, was examined by flow cytometry in ODN2006 (TLR9)-stimulated peripheral blood mononuclear cells and magnetically-isolated cells. Th1 cells, Th17 cells and NKT were also measured. RESULTS: Ex vivo stimulated cell analysis identified that post-apremilast (IL-10+CD19+) B10 cells were increased in all PsA and psoriasis patients and correlated with psoriatic skin and joint clinical improvement. Apremilast decreased IFNγ(+) T and NKT cells and IL-17(+)NKT cells. B10 cells also inversely correlated with Th1 cells, and IFNγ(+)NKT cells. CONCLUSION: These results suggest that Breg cells are a major target of apremilast in PsA and psoriasis and that apremilast-induced increase of Breg cells is associated with a decrease of Th1 cells, IFNγ-producing NKT cells and IL-17-producing NKT cells.

Platelets in Systemic Sclerosis: the Missing Link Connecting Vasculopathy, Autoimmunity, and Fibrosis?

PURPOSE OF REVIEW: Platelets are no longer recognized solely as cell fragments regulating hemostasis. They have pleiotropic functions and they are linked directly or indirectly with the three cornerstones of systemic sclerosis (SSc): vasculopathy, autoimmunity, and fibrosis. In this review, we summarize the current knowledge on the potential role of platelets in the pathogenesis of SSc. RECENT FINDINGS: Experimental evidence suggests that vasculopathy, a universal and early finding in SSc, may activate platelets which subsequently release several profibrotic mediators such as serotonin and transforming growth factor ß (TGFß). Platelets may also cross-react with the endothelium leading to the release of molecules, such as thymic stromal lymphopoietin (TSLP), that may trigger fibrosis or sustain vascular damage. Finally, activated platelets express CD40L and provide costimulatory help to B cells, something that may facilitate the breach in immune tolerance. Preclinical studies point to the direction that platelets are actively involved in SSc pathogenesis. Targeting platelets may be an attractive therapeutic approach in SSc.

The Greek (Hellenic) rheumatology over the years: from ancient to modern times.

Rheumatology has its roots in ancient Greece. Hippocrates and other prominent Greek (Hellenes) physicians in ancient times, Hellenistic, Roman, and Byzantine period were acute observers of disease course and of patients and were able to define many disorders. They wrote books on various aspects of medicine and these writings were the basis of medical practice and education in Europe and the Arabic world well into the seventeenth century. In 1821, Greece emerged from a long occupation by the Turks. In 1930, Adamantiades, a Greek Ophthalmologist, before Behcet of Turkey, described what is known as (Adamantiades)-Behcet disease. The first scientific Hellenic Society for Rheumatology (ERE) was established in 1960 and today ERE having been merged with the Professional Union of Greek rheumatologists (EPERE) is known as ERE-EPERE. Rheumatology is a strong specialty with 348 rheumatologists for a population of around 11 million. Greek rheumatologists have contributed to rheumatology science and practice, and are active physicians participating in the American College of Rheumatology and the EULAR annual congresses and in many educational postgraduate courses. ERE-EPERE formed therapeutic protocols for inflammatory and autoimmune rheumatic diseases which were incorporated in the electronic National prescription system. Rheumatologists are authorized to use this platform to prescribe biologicals free of charge for patients. ERE-EPERE publishes a peer-reviewed English language journal, the Mediterranean Journal of Rheumatology (MJR), an open access journal with no publication fees. MJR is a quarterly journal with international Editorial Board.

Targeting very early systemic sclerosis: a case-based review.

It is unknown whether treatment in very early/early systemic sclerosis (SSc) can affect long-term outcomes. A case-based review was conducted (i) to assess the effect of rituximab (RTX) in very early SSc and (ii) to explore how many clinical trials in SSc targeted early disease and whether treatment of these patients led to better clinical outcomes. We identified cases of very early SSc from our department and performed a search in MEDLINE and Scopus databases for clinical trials in SSc during 2005-2018. Two cases are reported where RTX was administered within 24 months from the appearance of Raynaud's. In the first case, there was an improvement in interstitial lung disease as indicated by the improvement in pulmonary function tests and the regression of changes in high-resolution chest computed tomography. In the second case, a good clinical response in skin fibrosis was observed. The review revealed the following: (i) only one-third of the studies were specifically designed to target early disease, (ii) there is confusion related to disease duration definition across SSc clinical trials but an obvious trend towards improvement was evident during the past years, (iii) the question of whether early implementation of therapy may lead to better clinical outcomes cannot be definitely answered based on existing data and (iv) there is still a very low level of incorporation of the new classification criteria in SSc trials. This review suggests that there may be a window of opportunity in SSc and highlights the need for clinical trials targeting very early/early disease.

Multiple hit infection and autoimmunity: the dysbiotic microbiota-ACPA connection in rheumatoid arthritis.

PURPOSE OF REVIEW: This review highlights the most recent data obtained in this field and provides clues toward the better understanding of the close interplay between microbiota and host, leading to autoimmune diseases. RECENT FINDINGS: A well-described model of microbiota/host interaction of relevance to autoimmunity is linking anti-citrullinated peptide antibody positive rheumatoid arthritis and alterations of microbiota largely concentrating on Porphyromonas gingivalis and more recently of Aggregatibacter actinomycetemcomitans and Prevotella copri. SUMMARY: The perception of the classical link between microbial infection and development of autoimmune disease has evolved to the more recent concept of the connection between the microbiome/dysbiosis and breaking of immunological tolerance.

Intestinal Involvement in Systemic Sclerosis: A Clinical Review.

Systemic sclerosis (SSc) is a chronic systemic disease characterized by microvasculopathy, autoantibodies, and extensive fibrosis. Intestinal involvement is frequent in SSc and represents a significant cause of morbidity. The pathogenesis of intestinal involvement includes vascular damage, nerve dysfunction, smooth muscle atrophy, and fibrosis, causing hypomotility, which leads to small intestinal bacterial overgrowth (SIBO), malabsorption, malnutrition, diarrhea, pseudo-obstruction, constipation, pneumatosis intestinalis, and fecal incontinence. Manifestations are often troublesome and reduce quality of life and life expectancy. Assessment of intestinal involvement includes screening for small intestine hypomotility, malnutrition, SIBO, and anorectal dysfunction. Current management of intestinal manifestations is largely inadequate. Patients with diarrhea are managed with low-fat diet, medium-chain triglycerides, avoidance of lactulose and fructose, and control of bacterial overgrowth with antibiotics for SIBO. In diarrhea/malabsorption, bile acid sequestrant and pancreatic enzyme supplementation may help, and nutritional support is needed. General measures are applied for constipation, and intestine rest plus antibiotics for pseudo-obstruction. Fecal incontinence is managed with measures for associated SIBO, or constipation, and with behavioral therapies. Pneumatosis intestinalis is usually an incidental finding that does not require any specific treatment. Immunomoduation should be considered early in intestinal involvement. Multidisciplinary approach of intestinal manifestations in SSc by gastroenterologists and rheumatologists is required for optimum management.

IL-10-producing regulatory B cells (B10 cells), IL-17+ T cells and autoantibodies in systemic sclerosis.

We aimed to analyze IL-10+ Breg (B10) cells, found to be reduced in systemic sclerosis (SSc), in relation to SSc-specific autoAbs and IL-17+ and IFNγ+ T cells in SSc. Peripheral blood B10 cells from 26 patients with SSc positive for anti-Topo I or anti-Cen autoAbs, and 12 healthy controls (HC) were studied by flow cytometry. IL-17+ and IFNγ+ T cells were also studied. B10 cells did not correlate with anti-Topo I or anti-Cen Ab levels but were inversely correlated with IL-17+ CD3+ cells and IFNγ+ CD3+ cells. IL-17+ CD3+ cells did not correlate with autoAb levels, but IFN-γ+ CD3+ cells were inversely correlated with anti-Topo I levels. In conclusion, in SSc, B10 cells did not correlate with SSc-specific autoAbs and exhibited an inverse correlation with IL-17+ T cells and IFNγ+ T cells.

IL-10 producing Bregs are impaired in psoriatic arthritis and psoriasis and inversely correlate with IL-17- and IFNγ-producing T cells.

Our aim was to study CD19(+)CD27(+)CD24(high) memory and CD19(+)CD24(high)CD38(high) transitional and IL-10+Breg cells, known to inhibit Th1 and Th17 cells in experimental arthritis, in psoriatic arthritis (PsA) and psoriasis (Ps). Peripheral blood Breg cells from 60 patients with PsA, 50 patients with Ps and 23 healthy controls were analyzed by flow cytometry. IL-17A-producing CD3(+) T cells and IFNγ-producing CD3(+) T cells and activation of p38 MAPK and STAT3 were also studied. CD19(+)CD27(+)CD24(high) and CD19(+)CD24(high)CD38(high) Breg cells were decreased in PsA and Ps. In Ps patients, CD19(+)CD27(+)CD24(high) Breg cells inversely correlated with PASI score. IL-10+Bcells were also decreased and inversely correlated with IL-17A+CD3+ and IFN-γ+CD3+ T cells. B cells from patients exhibited impaired activation of p38 MAPK and STAT3. In conclusion, IL-10+Breg cells are decreased PsA and Ps and inversely correlated with the severity of psoriasis and IL-17A+ and IFNγ+ T cells.

From microbiome to infectome in autoimmunity.

PURPOSE OF REVIEW: The current review discusses the pros and cons of the microbiome studies conducted in search of the association between microbiota and autoimmunity. RECENT FINDINGS: We focus on the role of infectome and autoinfectome as a bridge to link the findings of microbiome studies with those emerging from investigations of the role of specific viruses and antiviral responses as triggers of autoimmunity (through various mechanisms such as molecular mimicry). The 'usual suspects', such as herpetoviruses and Escherichia coli, are thoroughly discussed in light of the data emerged by the microbiome studies, using as examples specific autoimmune rheumatic diseases and inflammatory bowel diseases. SUMMARY: We conclude that the studies of the oral cavity, gastrointestinal, and urinary tract microbiome are informative but can only be useful if further explored from the infectome perspective. This means that the plethora of bacteria associated with autoimmune diseases from microbiome studies can be and must be tested experimentally. If certain bacteria are associated directly or indirectly with autoimmune diseases, specific immunological mechanisms must be identified.