Immune Complex-mediated Diseases Research Articles

Clinicopathological Features of Membranous Nephropathy Complicated by IgA Nephropathy: A Retrospective Analysis of Seven Cases.

Aims/Background Both membranous nephropathy (MN) and immunoglobulin A nephropathy (IgAN) are immune complex-mediated glomerular diseases, but the concurrent occurrence of these two conditions in the same patient is not common, a phenomenon that is currently not supported by clinical data in terms of treatment and prognosis. This study explores the clinical and pathological characteristics, as well as the treatment outcomes, of patients affected by MN and IgAN simultaneously. Methods The clinical data, pathological features, and diagnostic and therapeutic information of seven cases of MN complicated by IgAN, treated between December 2015 and December 2022, were retrospectively analyzed. Results Among the seven cases, there were two male and five female patients, with an average age of 57.3 ± 9.2 years. All patients presented with clinical manifestations of proteinuria and edema upon admission, with an average 24-hour urine protein of 3716.6 ± 1519.4 mg/24 h. Phospholipase A2 receptor (PLA2R) expression was detected in all seven cases, and nephrotic syndrome was clinically diagnosed in five cases. Additionally, all seven cases showed microscopic hematuria, with intermittent gross hematuria in two cases. All seven patients included in this study underwent renal biopsy. After disease staging, the patients had MN stages I-III and IgAN stages II-III. Pathological findings revealed abnormal glomerular basement membrane (GBM) and diffuse immunoglobulin G (IgG) deposition in the subepithelial space, predominantly of the IgG4 subtype. Simultaneously, there was diffuse mesangial zone deposition of immunoglobulin A (IgA) to varying degrees, co-localization of complement component C3 and IgA, and mesangial cell proliferation. Treatment strategies included angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) in combination with steroids or immunosuppressive therapies such as tacrolimus, cyclophosphamide, and rituximab. After 2-6 months of treatment, all patients achieved complete remission with a favourable prognosis. Conclusion MN accompanied by IgAN tends to occur more frequently in middle-aged and elderly individuals, with a relatively low incidence. The latent feature of the comorbidities manifests as a form of IgAN superimposed on the background of MN. Utilizing ACEI or ARB in combination with steroids or various immunosuppressive therapies represents a potentially effective treatment strategy.

Rheumatoid Arthritis and COVID-19 at the Intersection of Immunology and Infectious Diseases: A Related PRISMA Systematic Literature Review.

Rheumatoid arthritis (RA) patients face different health challenges when infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) than the general population, due to both their immunocompromised state and the immunosuppressive therapies they receive. This systematic literature review, which follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) paradigm, explores the interactions between RA and SARS-CoV-2 infection, focusing on immunologic issues, disease management, vaccination, and adverse outcomes. In order to obtain the most relevant information, we systematically reviewed the specific literature from 1 January 2021 to 31 December 2023, based on the PRISMA method, by which we eventually selected 35 eligible articles, to which we added other ISI-indexed studies to enrich our results further. Consequently, we performed a funnel analysis to evaluate the potential for publication bias. Firstly, the data collected revealed the impact of the pandemic on RA diagnoses and the fear of face-to-face medical consultations that delayed adequate treatment. Secondly, cardiovascular and metabolic comorbidities increase the risk of prolonged COVID-19 symptoms, hospitalization, and severe COVID-19 outcomes for RA patients. With respect to immunosuppressive treatment used to control RA, it was observed that glucocorticoids (especially high-dose usage) and Rituximab (RTX) predispose the patients to poor SARS-CoV-2 outcomes, as opposed to Baricitinib and interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) inhibitors. COVID-19 vaccination has proven effective and generally safe for RA patients in some studies, although therapies with Methotrexate (MTX), Abatacept (ABA), and RTX have been associated with impaired vaccine immune response. This systematic literature review brings updated and thorough information with respect to the immunological, clinical, and management of a complex immune-mediated inflammatory disease (IMID) like RA in the setting of COVID-19 and underlines the challenges faced by this group of patients. The lessons learned can be extended beyond the pandemic in shaping a more informed and compassionate healthcare system and offering long-term medical care for patients with RA.

Evaluating Experiences in a Digital Nutrition Education Program for People With Multiple Sclerosis: A Qualitative Study.

Multiple sclerosis (MS) is a complex immune-mediated disease with no currently known cure. There is growing evidence to support the role of diet in reducing some of the symptoms and disease progression in MS, and we previously developed and tested the feasibility of a digital nutrition education program for people with MS. The aim of this study was to explore factors that influenced engagement in the digital nutrition education program, including features influencing capability, opportunity and motivation to change their dietary behaviours. Semi-structured interviews were conducted with people who had MS, and who completed some or all of the program until data saturation was reached. Interviews were analysed inductively using thematic analysis. Themes were deductively mapped against the COM-B (Capability, Opportunity, Motivation, Behaviour) behaviour change model. Sixteen interviews were conducted with participants who completed all (n = 10) or some of the program (n = 6). Four themes emerged: (1) acquiring and validating nutrition knowledge; (2) influence of time and social support; (3) getting in early to improve health and (4) accounting for food literacy experiences. This is the first online nutrition program with suitable behavioural supports for people with MS. It highlights the importance of disease-specific and evidence-based nutrition education to support people with MS to make dietary changes. Acquiring nutrition knowledge, coupled with practical support mechanisms, such as recipe booklets and goal setting, emerged as crucial for facilitating engagement with the program. When designing education programs for people with MS and other neurological conditions, healthcare professionals and program designers should consider flexible delivery and building peer support to address the needs and challenges faced by participants. Members of the MS Nutrition Research Program Stakeholder Reference Group, which includes people with MS and MS health professionals, provided input during the development of the nutrition education program and study design stages.

Biomarkers in Psoriasis: The Future of Personalised Treatment.

Psoriasis is a chronic and complex immune-mediated papulosquamous disease affecting almost 2% of the world population. The interaction between a genetically predisposed individual and environmental triggers leads to a vicious cycle involving autoreactive T cells, dendritic cells, keratinocytes and dermal cells. Up to 40% of the psoriasis cases develop disabling psoriatic arthritis and an equal number of patients also tend to develop metabolic syndrome as well as cardiovascular comorbidities; hence, this is no more considered to be a disease limited to skin only. Being a systemic disease, there is an urgent need to develop potential biomarkers for the assessment of disease severity, prediction of outcome of the therapeutic intervention and association with various systemic comorbidities. Diverse genetic markers not only function as predictors of diseases pathogenesis, but also help to predict development of psoriasis and psoriatic arthritis. Personalised medicine is customising the therapeutic needs of a psoriasis patient and improving the outcome as per the hints we receive from the various biomarkers. This review deals with the list of potential biomarkers proposed to be useful in psoriasis, though there is limited data validating their routine use in clinical practice and the progress so far made in the field of precision medicine for psoriasis.

Immune mechanisms of granuloma formation in sarcoidosis and tuberculosis.

Sarcoidosis is a complex immune-mediated disease characterized by clusters of immune cells called granulomas. Despite major steps in understanding the cause of this disease, many questions remain. In this Review, we perform a mechanistic interrogation of the immune activities that contribute to granuloma formation in sarcoidosis and compare these processes with its closest mimic, tuberculosis, highlighting shared and divergent immune activities. We examine how Mycobacterium tuberculosis is sensed by the immune system; how the granuloma is initiated, formed, and perpetuated in tuberculosis compared with sarcoidosis; and the role of major innate and adaptive immune cells in shaping these processes. Finally, we draw these findings together around several recent high-resolution studies of the granuloma in situ that utilized the latest advances in single-cell technology combined with spatial methods to analyze plausible disease mechanisms. We conclude with an overall view of granuloma formation in sarcoidosis.

The Influence of Adipokines on Radiographic Damage in Inflammatory Rheumatic Diseases

Inflammatory rheumatic diseases (IRDs) are complex immune-mediated diseases that are characterized by chronic inflammation of the joints. Rheumatoid arthritis (RA) and spondyloarthritis (SpA), including axial SpA (ax SpA) and psoriatic arthritis (PsA), are the most common forms of IRD. Both RA and ax SpA are characterized by a chronic course with progressive structural modifications, namely, cartilage damage and bone erosions in RA and osteoproliferative changes with spinal ossifications in ax SpA. The adipose tissue is involved in the pathophysiology of IRDs via the release of several proteins, namely, adipokines. Several adipokines with pro-inflammatory effects have been identified, such as leptin, adiponectin, visfatin and resistin. In this review, we discuss the role that adipokines may play in the structural modifications of the peripheral joints and/or axial skeleton. In RA, the role of leptin in structural damage remains controversial, while adiponectin and its high-molecular-weight isoform are known to have an influence on the development of bone erosions and radiographic progression. Resistin also appears to be a potent detrimental adipokine for the joints in RA. In ax SpA, visfatin seems to be an attractive candidate for radiographic progression, while leptin and adiponectin have negative effects on radiographic progression.

DOP51 Mucosa-associated microbial signatures associate with objective response prior to the start of anti-TNFα but not vedolizumab or ustekinumab in Crohn’s disease patients

Abstract Background Crohn’s disease (CD) is a complex immune-mediated disease of the gastrointestinal tract where the gut microbiome plays an important role. Current biological treatment options in CD include the anti-TNFα agents adalimumab (ADA) and infliximab (IFX), vedolizumab (VDZ), and ustekinumab (USTE). Finding biomarkers to predict therapy response is still a clinical unmet need, as the majority of CD patients fail to reach endoscopic remission within 1 year of treatment. While the majority of studies focus on fecal samples, mucosa-adherent bacterial signature could bring forth stable biomarkers. In this study, we sought to identify signatures of the adherent microbiome in intestinal biopsies aimed at differentiating responders (R) from non-responders (NR), prior to the start of biological treatment. Methods We prospectively collected paired ileal and colonic biopsies (stored snapfrozen in -80 ºC) from adult CD patients scheduled to start anti-TNFα (IFX and ADA), VDZ and USTE treatment during baseline endoscopies. After 6-12 months of follow-up, patients were classified as either R or NR based on endoscopic response (≥50% reduction in SES-CD score) in combination with steroid-free clinical response (≥3 point drop in HBI or HBI ≤4) and/or biochemical response (≥50% reduction in C-reactive protein (CRP) and fecal calprotectin or a basal CRP ≤5 g/mL and fecal calprotectin ≤250 µg/g). Microbiome composition of the biopsies was determined using 16S RNA gene V3V4 amplicon sequencing. Results For the anti-TNFα cohort, we included in total 36 CD patients (21R and 18 NR), for VDZ cohort a total of 44 patients (28 R and 16 NR) and for USTE cohort a total of 40 patients (20R and 20 NR).When comparing α-diversity and β-diversity between R and NR, we did not find significant differences in ileal and colonic samples at baseline for the VDZ and USTE cohorts. Notable, for the anti-TNFα cohort (table 1), we obtained significant differences when comparing α-diversity (p=0.028) and β-diversity between R and NR. We demonstrated differences between colonic R and NR in taxa abundance for ASVs associated with the phyla Bacteroidetes, Firmicutes, Fusobacteria, Proteobacteria (figure 1). Furthermore, ASVs associated with Firmicutes, Bacteroidetes, Actinobacteria are different in abundance between ileal R and NR (figure 2). Figure 1: Differential taxa abundance colonic R vs NR anti-TNFα Figure 2: Differential taxa abundance ileal R vs NR anti-TNFα Figure 3: graphical summary Conclusion Here, we investigated the microbial signature of R and NR before the start of treatment of three separate cohorts and we demonstrated that the mucosa-associated microbiome differentiates R and NR to anti-TNFα therapy. Further analyses as part of the EPIC Pioneer study, are ongoing.

Methyl Gallate Alleviates Acute Ulcerative Colitis by Modulating Gut Microbiota and Inhibiting TLR4/NF-κB Pathway.

Ulcerative colitis (UC) is a complex immune-mediated inflammatory disease. In recent years, the incidence of UC has increased rapidly, however, its exact etiology and mechanism are still unclear. Based on the definite anti-inflammatory and antibacterial activities of Sanguisorba officinalis L., we studied its monomer, methyl gallate (MG). In this study, we employed flow cytometry and detected nitric oxide production, finding MG regulated macrophage polarization and inhibited the expression of proinflammatory cytokines in vitro. MG also exhibited anti-inflammatory activity accompanying with ameliorating body weight loss, improving colon length and histological damage in dextran sulfate sodium-induced UC mice. Meanwhile, transcription sequencing and 16S rRNA sequencing analyzed the key signaling pathways and changes in the gut microbiota of MG for UC treatment, proving that MG could alleviate inflammation by regulating the TLR4/NF-κB pathway in vivo and in vitro. Additionally, MG altered the diversity and composition of the gut microbiota and changed the abundance of metabolic products. In conclusion, our results are the first to demonstrate that MG has obvious therapeutic effects against acute UC, which is related to macrophage polarization, improved intestinal flora dysbiosis and inhibition of TLR4/NF-κB signaling pathway, and MG may be a promising therapeutic agent for UC treatment.

Considerations when starting patients on multiple biologics and small molecules.

Inflammatory bowel disease (IBD) is complex disease that poses significant economic, and psychological burden on patients. Despite advent of newer biologics and small molecules targeting different aspects of immunopathogenesis, there appears to be a plateau in clinical outcomes. In this review we discuss the role of multiple biologics, existing evidence and various considerations when prescribing multiple biologics. Recent scientific advances helped to unravel the pathophysiology of inflammatory bowel disease and newer cytokines have been identified which can be potential targets in the management of IBD. Targeting more than one cytokine appears to be logical solution to break the therapeutic ceiling to improve clinical outcomes in IBD. The combination biologics appear safe and effective; however, the available evidence is limited. Refractory IBD, presence of other immune mediated inflammatory diseases and extra intestinal manifestations are currently the common considerations of combination biologics in IBD. Inflammatory bowel disease is a complex immune mediated disease with diverse clinical presentation and often has a complicated clinical course requiring multidisciplinary management. As the number of targeted therapies increases so does the concern on their safety and efficacy. Combination biologics though may appear to be safe, we need well designed prospective studies for firm conclusions.

Omalizumab for the management of refractory chronic spontaneous urticaria

Chronic spontaneous urticaria (CSU) is a heterogeneous, systemic, primarily mast cell-driven disease with sudden appearance of wheals with or without angioedema with pruritus for more than 6 weeks. It affects 0.3%–0.6% of the general population. CSU is a complex immune-mediated disease due to induction of basophil and mast cell degranulation with more than one mechanism of auto-allergy Type I (mediated by specific immunoglobulin E (IgE) targeting auto-allergens as thyroperoxidase, etc.) and auto-immunity Type II (mediated by IgG auto-antibodies binding to alpha-subunit of high affinity IgE receptor [FcERI]) with increased expression of Type II cytokines and activation of coagulation cascade. Pruritus is due to sensory nerve activation by histaminergic pathway (Histamine receptors- H1R and H4R) and histamine-independent pathway (Substance P, Capsacin, and Reactive oxygen species, etc.). The international guidelines on CSU recommend to treat CSU until it is gone. The use of second-generation anti-histamine in effective dose as the first-line treatment and up-dosing of second generation (SgAH) up to four-fold is recommended in treatment-resistant patients. The humanized anti-IgE monoclonal antibody Omalizumab has been shown to have both excellent safety profiles as the only third-line treatment option in anti-histamine-resistant urticaria (approved by United States Food and Drug Administration in August, 2014). However, there are several questions to be answered with reference to the optimal dose, duration, and the rates of long-term remission with omalizumab. Other biologics as Ligelizumab are less well studied but have an important role in the specific type of omalizumab-resistant CSU. In this review, we will summarize the role of omalizumab in anti-histamine resistant CSU.

The burden of progression of psoriatic arthritis. All-Russian register data

Psoriatic arthritis (PsA) is a complex immune-mediated disease in which a third of patients with psoriasis (PsO) have a inflammatory lesion of both the musculoskeletal system (peripheral joints and axial structures) and extra-articular manifestations (dactylitis, enthesitis, nail PsO, uveitis and inflammatory bowel disease). To assess the burden of PsA progression in real practice according to the Russian register of PsA patients. Seven hundred thirty seven M/F=350 (47.5%)/387 (52.5%) patients with PsA from the Russian register of PsA patients were included. Mean age 47.412.7 yrs., duration of PsO 200.6158.9 mo., PsA 79.681.9 mo. All patients were divided into 2 groups by PsA duration: 1st gr 36 mo 288 (39.1%) and 2nd gr 36 mo 449 (60.9%). All patients underwent standard clinical examination of PsA activity. Tender (68) and swelling (66) joint count (TJC, SJC), DAPSA, LEI, tenderness of the plantar fascia, PsO BSA (%), PASI, HAQ-DI, PsAID-12, BMI (kg/m2), ESR (mm/h), CRP (mg/l) and comorbidities by ICD-10 were evaluated. Parametric and non-parametric methods of statistical analysis were used. All p0.05 were considered to indicate statistical significance. In patients with PsA duration 36 mo we found significant prevalence of erosions by X-Ray, axial PsA, BMI30 kg/m2, HAQ-DI1, PsAID-124, arterial hypertension, metabolic syndrome and overall comorbidity (p0.05). There were no significant differences between groups in PsO severity by BSA3%, PASI1, LEI1, TJC, SJC, dactylitis, ESR30 mm/h, CRP10 mg/l, DAPSA, diabetes mellitus, hyperlipidemia, coronary heart disease and liver damage (p0.05). Сonclusion. Long-standing stage PsA is associated with erosions, axial PsA, worst health related quality of life, functional disability and increased cardio-metabolic disorders and overall comorbidity. Our results support the idea to start bDMARDs at early stage of PsA, it can improve better outcomes.

A Case Report on Autoimmune Hepatitis

Background: Autoimmune Hepatitis (AIH) is associated with chronic growing hepatic disease and a complex immune-mediated hepatic disease investigated histologically by the broad level of aminotransferase, autoantibodies, hypergammaglobulinemia and interface hepatitis. AIH affects all ages male and female, worldwide, regardless of sex. It is a rare chronic hepatic inflammation with unclear ethology. In most cases, autoimmune diseases are predominant in females less than 0.02. Case Presentation: A 4 year-old-male patient from Yawatmal, the patient was admitted to the paediatric ward to AVBRH, Sawangi Meghe, Wardha. The patient was diagnosed with the case of autoimmune hepatitis. The patient suffered from chief complaints of difficulty in generalized weakness and fever from 2 days, nausea and vomiting with no other complaints. no past medical history noted of diabetes mellitus, asthma, COVID 19, or having no any other congenital physical abnormalities. Conclusion: Autoimmune hepatitis is the rare chronic inflammatory liver disease usually seen all age groups of people especially as compared to males. The care has been given to the patient in accurate diagnosis through investigation, such as blood investigations, radiological investigation, histopathological investigation, abdomen, and pelvic radiology. Because of this investigation, confirms that whether it is autoimmune hepatitis or not. A patient is undergoing this autoimmune hepatitis treatment and also further medical management should be taken.

Rheumatoid arthritis: Evolving recognition of a common disease

Rheumatoid arthritis (RA) is a highly prevalent autoimmune disease and the most common form of autoimmune inflammatory arthritis. Studies of RA pathogenesis have contributed significantly to understanding the basis for complex immune-mediated disease, identified key steps in the development of autoimmune activation and joint damage in RA, and led to the development of targeted therapies that opened up the era biologic therapy. Current studies are linking differences in gene expression to abnormalities in cellular function that will help optimize therapy for individual patients and advance the goal of personalized medicine. Our evolving understanding and current important issues in RA are highlighted.

A specific microbiota signature is associated to various degrees of ulcerative colitis as assessed by a machine learning approach

ABSTRACT Ulcerative colitis (UC) is a complex immune-mediated disease in which the gut microbiota plays a central role, and may determine prognosis and disease progression. We aimed to assess whether a specific microbiota profile, as measured by a machine learning approach, can be associated with disease severity in patients with UC. In this prospective pilot study, consecutive patients with active or inactive UC and healthy controls (HCs) were enrolled. Stool samples were collected for fecal microbiota assessment analysis by 16S rRNA gene sequencing approach. A machine learning approach was used to predict the groups’ separation. Thirty-six HCs and forty-six patients with UC (20 active and 26 inactive) were enrolled. Alpha diversity was significantly different between the three groups (Shannon index: p-values: active UC vs HCs = 0.0005; active UC vs inactive UC = 0.0273; HCs vs inactive UC = 0.0260). In particular, patients with active UC showed the lowest values, followed by patients with inactive UC, and HCs. At species level, we found high levels of Bifidobacterium adolescentis and Haemophilus parainfluenzae in inactive UC and active UC, respectively. A specific microbiota profile was found for each group and was confirmed with sparse partial least squares discriminant analysis, a machine learning-supervised approach. The latter allowed us to observe a perfect class prediction and group separation using the complete information (full Operational Taxonomic Unit table), with a minimal loss in performance when using only 5% of features. A machine learning approach to 16S rRNA data identifies a bacterial signature characterizing different degrees of disease activity in UC. Follow-up studies will clarify whether such microbiota profiling are useful for diagnosis and management.

First Reported Incidence of Delayed Secondary Abdominal Compartment Syndrome in a Trauma Patient with Scleroderma: A Case Report and Review of the Literature

Background: Scleroderma is a complex immune-mediated rheumatic disease that is characterized by fibrosis of the skin, internal organs, and vasculopathy. Extensive fibrosis, especially in the limited compartment, has been reported to induce acute compartment syndrome frequently reported involving the upper and lower extremities. Case Presentation: We present a rare case of a 54-year-old Caucasian female who underwent surgery for abdominal compartment syndrome in the setting of scleroderma. Upon arrival, at the hospital, the patient’s health status showed signs of improvement with no indicators of abdominal compartment syndrome until the tenth hospital day. A CT scan showed a new intra-abdominal fluid collection with total lower abdominal anasarca and a stable retroperitoneal hematoma. Following emergency surgery, significant bowel edema without other intra-abdominal injuries was noted. Conclusion: Secondary abdominal compartment syndrome may occur in patients with scleroderma without evidence of intra-abdominal trauma or emergent abdominal surgery. Further research is warranted to investigate the relationship between scleroderma and secondary abdominal compartment syndrome.

First-in-class topical therapeutic omilancor ameliorates disease severity and inflammation through activation of LANCL2 pathway in psoriasis

Psoriasis (PsO) is a complex immune-mediated disease that afflicts 100 million people. Omilancor is a locally-acting, small molecule that selectively activates the Lanthionine Synthetase C-like 2 (LANCL2) pathway, resulting in immunoregulatory effects at the intersection of immunity and metabolism. Topical omilancor treatment in an imiquimod-induced mouse model of PsO ameliorates disease severity, epidermal hyperplasia and acanthosis. Further, pharmacological activation of LANCL2 results in significant downregulation of proinflammatory markers including local reduction of IL17, and infiltration of proinflammatory cell subsets. These therapeutic effects were further validated in an IL-23 PsO model. This model reported increased preservation of homeostatic skin structure, accompanied by a decreased infiltration of proinflammatory T cell subsets. In CD4+ T cells and Th17 cells, the LANCL2 pathway regulates proinflammatory cytokine production, proliferation and glucose metabolism. Metabolically, the loss of Lancl2 resulted in increased glycolytic rates, lactate production and upregulated enzymatic activity of hexokinase and lactate dehydrogenase (LDH). Inhibition of LDH activity abrogated the increased proliferation rate in Lancl2−/− CD4+ T cells. Additionally, topical omilancor treatment decreased the metabolic upregulation in keratinocytes, keratinocyte hyperproliferation and expression of inflammatory markers. Omilancor is a promising topical, LANCL2-targeting therapeutic candidate for the treatment of PsO and other dermatology indications.

Gender and the Sex Hormone Estradiol Affect Multiple Sclerosis Risk Gene Expression in Epstein-Barr Virus-Infected B Cells

Multiple Sclerosis (MS) is a complex immune-mediated disease of the central nervous system. Treatment is based on immunomodulation, including specifically targeting B cells. B cells are the main host for the Epstein-Barr Virus (EBV), which has been described as necessary for MS development. Over 200 genetic loci have been identified as increasing susceptibility to MS. Many MS risk genes have altered expression in EBV infected B cells, dependent on the risk genotype, and are themselves regulated by the EBV transcription factor EBNA2. Females are 2-3 times more likely to develop MS than males. We investigated if MS risk loci might mediate the gender imbalance in MS. From a large public dataset, we identified gender-specific associations with EBV traits, and MS risk SNP/gene pairs with gender differences in their associations with gene expression. Some of these genes also showed gender differences in correlation of gene expression level with Estrogen Receptor 2. To test if estrogens may drive these gender specific differences, we cultured EBV infected B cells (lymphoblastoid cell lines, LCLs), in medium depleted of serum to remove the effects of sex hormones as well as the estrogenic effect of phenol red, and then supplemented with estrogen (100 nM estradiol). Estradiol treatment altered MS risk gene expression, LCL proliferation rate, EBV DNA copy number and EBNA2 expression in a sex-dependent manner. Together, these data indicate that there are estrogen-mediated gender-specific differences in MS risk gene expression and EBV functions. This may in turn contribute to gender differences in host response to EBV and to MS susceptibility.

Breast involvement in granulomatosis with polyangiitis: a case report

BackgroundGranulomatosis with polyangiitis (GPA) previously known as Wegener's granulomatosis is a rare complex immune-mediated disease and a multisystem disorder with varying presentations where many of the imaging features of GPA overlap with those of other diseases, and hence its diagnosis can be challenging.Case presentationHere we report a case of a 48-year-old female who presented with complaints of hemoptysis, difficulty in speech, bilateral progressive hearing loss and, a palpable lump in the right breast. The case was initially misdiagnosed as breast carcinoma but biopsy proved to be GPA. Here we present the multisystem manifestations of GPA involving the head and neck, breast, lungs, spleen with involvement of the breast being very rare. The breast lesion showed improvement with steroids on follow-up.ConclusionsGPA is a multisystem disease and though breast lesions in GPA are rare, a thorough knowledge about this uncommon manifestation is required and clinical, radiological, and histopathological correlation is of utmost importance in the evaluation of a breast lesion in cases of multisystem involvement to avoid unnecessary surgeries. The differential diagnosis of breast tumors should include such rare conditions that can sometimes mimic breast cancer. Early diagnosis and initiation of the immunosuppressive treatment help in a better prognosis of the disease.

CD30L+ classical monocytes play a pro-inflammatory role in the development of ulcerative colitis in patients

Ulcerative colitis (UC) is a chronic idiopathic inflammatory bowel disease that affects the large intestine and exhibits a relapsing and remitting course. It is a complex immune-mediated disease of the gastrointestinal tract that increases morbidity and negatively influences the quality of life. Although our previous studies have indicated that CD30L is involved in the adaptive immune response in UC, it remains unclear whether it participates in the innate immune response. Our results revealed that the CD30L level significantly increased in the circulating classical monocytes of patients with UC and showed a positive correlation with the severity of UC. CD30L may participate in monocyte-mediated inflammation in patients with UC through the activation of circulating classical monocytes. The present study provides insights into a marker of severity and a potential target for the development of immunological therapy of UC.

P034 Parvovirus B19 infection causing vasculitis and hypocomplementemia

Abstract Background/Aims Acquired hypocomplementemia occurs through immune complex-mediated diseases, as seen in systemic lupus erythematosus (SLE), idiopathic membranoproliferative glomerulonephritis (MPGN) and cryoglobulinemia. Infective causes are less common, although chronic bacterial and viral infections causing glomerulonephritis (GN) and vasculitis have been reported. Bacterial infections causing chronic osteomyelitis, endocarditis and visceral abscesses have all been implicated, whilst hepatitis B is the only virus known to cause severe GN/ vasculitis leading to low complement levels. Severe meningococcal disease is an established cause of acquired hypocomplementemia, typically associated with Nisseria Meningitidis. Parvovirus B19 is an infection exclusive to humans, usually manifesting as fifth disease, a mild illness characterised by a rash, fever and runny nose. Less common systemic effects include hydrops fetalis, thrombocytopenia, neutropenia, neurological sequalae (including encephalopathy, aseptic meningitis, neuropathy and neuralgic amyotrophy), myocarditis and hepatitis. Arthropathy is by far the most common manifestation in adults, affecting 60% of females and 30% of males. Methods The literature on Parvovirus B19 and hypocomplementemia is sparse, limited to case reports and comparative studies, the pathogenicity of which stems from glomerulonephritis, consequently resulting in low complement levels. We present a case series of 2 patients with Parvovirus B19 infection and acquired hypocomplementemia between 2016-2020. Results Patient A, a 26-year-old female, presented with a vasculitic rash on her legs and arthralgia affecting her hands and knees, refractory to oral prednisolone and hydroxychloroquine. She was found to have low complement levels (C3 0.61 g/l and C4 0.03 g/l), whilst ANA, ENA and ANCA testing was negative. She also had a negative rheumatoid factor and anti-CCP antibody, and a normal serum protein: creatinine (6 mg/mmol). Immunoglobulins were within normal range (IgG 8.7 g/l, IgA 0.80 g/l, IgM 2.41 g/l) and a serum protein electrophoresis was normal. Hepatitis and HIV serology was also negative. Patient B, a 34-year-old female, 9 weeks pregnant, presented with polyarthralgia, fever and a maculopapular rash, with normal inflammatory markers and a normal serum protein: creatinine (9 mg/mmol). Her complement was low (C3 0.57 g/l and C4 <0.02 g/l), ANA weakly positive, ENA negative and her ANCA screen showed a pANCA pattern with positive anti-PR3 antibodies (4.6 U/ml). She also had weakly positive dsDNA antibodies (37 IU/ml), and smooth muscle antibodies were weakly positive on tissue biopsy. Anti-C1q antibodies were normal. IgM was raised (2.56 g/l), whilst IgG and IgA were normal (10.8 g/l and 1.37 g/l, respectively). Serum protein electrophoresis was normal. HIV, hepatitis B and syphilis serology was all negative. In both cases, Parvovirus B19 IgM antibody was detected. Conclusion We recommend that clinicians consider acute viral illness in patients presenting with vasculitis and hypocomplementemia. If diagnosis and treatment can be established early, patients can avoid the need for long term immunosuppression. Disclosure A. Gharatya: None. C. Nelson: None. S. Melath: None.