Ophthalmologic profile of patients with systemic sclerosis.

PURPOSE: To study the ophthalmologic manifestations of systemic sclerosis (SSc) and its correlation with autoantibody profile. METHODS: A cross-sectional study on 200 eyes of 100 consecutive adult patients diagnosed with SSc was performed at a tertiary care center in Northern India. The examination of ocular adnexa, anterior segment, and posterior segment with slit-lamp biomicroscopy, tear film break-up time (TBUT), Schirmer's II test, and choroidal thickness measurement by swept-source ocular coherence tomography was done. Autoantibody profile was available for 85 patients, and its statistical association with the ocular examination findings was analyzed. RESULTS: In total, 100 patients (93 females and 7 males) were included. The mean age was 45.11 ± 11.68 years, and the mean disease duration was 6.93 ± 3.68 years. Meibomian gland disease was more commonly found in patients with the diffuse subtype of SSc (P = 0.037). Choroidal thickness was increased in 34% and decreased in 7% (reference range = 307 ± 79 mm) patients. Reduced TBUT, meibomian gland dysfunction, and eyelid stiffness had a statistically significant association with the presence of anti-Scl-70 antibody (P = 0.003, <0.0001, and 0.004, respectively). These patients had ocular fatigue, foreign body sensation, and burning sensation. No significant association was noted with the presence of SS-A/Ro and SS-B/La antibodies. CONCLUSION: This study highlights the need for an active comprehensive ophthalmic evaluation. Approximately 75% of the patients in our cohort had ocular involvement to varying extent. An isolated presence of anti-Scl70 antibody was also found to have a positive association with dry eye disease.

Shared and distinct genetics of pure type 1 diabetes and type 1 diabetes with celiac disease, homology in their auto-antigens and immune dysregulation states: a study from North India.

AIM: This study was undertaken to explicate the shared and distinctive genetic susceptibility and immune dysfunction in patients with T1D alone and T1D with CD (T1D + CD). METHODS: A total of 100 T1D, 50 T1D + CD and 150 healthy controls were recruited. HLA-DRB1/DQB1 alleles were determined by PCR-sequence-specific primer method, SNP genotyping for CTLA-4 and PTPN22 was done by simple probe-based SNP-array and genotyping for INS-23 Hph1 A/T was done by RFLP. Autoantibodies and cytokine estimation was done by ELISA. Immune-regulation was analysed by flow-cytometry. Clustering of autoantigen epitopes was done by epitope cluster analytical tool. RESULTS: Both T1D alone and T1D + CD had a shared association of DRB1*03:01, DRB1*04, DRB3*01:07/15 and DQB1*02. DRB3*01:07/15 confers the highest risk for T1D with relative risk of 11.32 (5.74-22.31). Non-HLA gene polymorphisms PTPN22 and INS could discriminate between T1D and T1D + CD. T1D + CD have significantly higher titers of autoantibodies, expression of costimulatory molecules on CD4 and CD8 cells, and cytokine IL-17A and TGF-ß1 levels compared to T1D patients. Epitopes from immunodominant regions of autoantigens of T1D and CD clustered together with 40% homology. CONCLUSION: Same HLA genes provide susceptibility for both T1D and CD. Non-HLA genes CTLA4, PTPN22 and INS provide further susceptibility while different polymorphisms in PTPN22 and INS can discriminate between T1D and T1D + CD. Epitope homology between autoantigens of two diseases further encourages the two diseases to occur together. The T1D + CD being more common in females along with co-existence of thyroid autoimmunity, and have more immune dysregulated state than T1D alone.

Major histocompatibility complex (MHC) gene frequency in acquired dermal macular hyperpigmentation: a case control study.

BACKGROUND: Human leukocyte antigen (HLA) allele frequencies have a known association with the pathogenesis of various autoimmune diseases. METHODS: We recruited 31 Indian patients of acquired dermal macular hyperpigmentation (ADMH) and 60 unrelated, age-and-gender-matched healthy controls. After history and clinical examination, 5 ml of blood in EDTA vials was collected. These samples were subjected to DNA extraction and the expression of HLA A, B, C, DR, DQ-A, and DQ-B was studied. RESULTS: There was a predominance of females with a gender ratio of 23 : 8 and the most common phototype was Fitzpatrick type IV (83.9%). There was a significant association of HLA A*03:01 (OR: 5.8, CI: 1.7-17.0, P = 0.005), HLA B*07:02 (OR: 5.3, CI: 1.9-14.6, P = 0.003), HLA C*07:02 (OR: 4.3, CI: 1.8-9.6, P = 0.001), HLA DRB1*10:01 (OR: 7.6, CI: 1.7-38.00, P = 0.022), and HLA DRB1*15:02 (OR: 31.0, CI: 4.4-341.8, P < 0.001) with patients compared to controls, whereas HLA DQB*03:01 was less associated with patients compared to controls (OR: 0.2, CI: 0.0-0.6, P = 0.009). CONCLUSION: Patients with ADMH are more likely to have the HLA A*03:01, HLA B 07*02, HLA C*07:02, HLA DRB1*10:01, HLA DRB1*15:02 and less likely to have the HLA DQB*03:01 allele. Larger cohort studies may thus be conducted studying these specific alleles.

Impact of Anti-nuclear Antibody Seropositivity on Clinicopathological Parameters, Treatment Response, and Survival in Lymphoma Patients.

PURPOSE: Lymphoproliferative disorders and autoimmune diseases both are interrelated. The high incidence of lymphoma in autoimmune diseases and frequent antinuclear antibody (ANA) positivity in lymphoma patients have been observed. But the impact of ANA positivity on various clinical parameters and responses to therapy has not been elucidated properly. METHODS: In the present study, 73 treatment-naive lymphoma patients were recruited prospectively and samples were collected at baseline and after completion of therapy for evaluation of ANA. Comparative analysis was performed for various parameters between ANA-positive and ANA-negative groups. RESULTS: The prevalence of ANA at baseline was 27% in lymphoma patients which further increased to 35% after chemotherapy. The ANA-positive group had a significantly higher mean age (58±14.7 vs 47±19.9; p=0.01), early stage (77% vs 38%; p=0.02,) and infrequent B-symptoms (25% vs 52%; p=0.03) as compared to ANA-negative group. No significant difference was observed in the response to therapy and survival (both event-free and overall survival). The most frequent ANA pattern was speckled (50%) at baseline, and homogenous (42%) after the therapy. CONCLUSION: ANA is more frequent in lymphoma and increases further after chemotherapy. Higher mean age, early stage, and infrequent B symptoms were found to be significantly more frequent in ANA-positive lymphoma patients; however, only limited evidence supports its role as a prognostic marker or response to therapy. A wider study with appropriate follow-up data and molecular assay could shed light on the immunobiology of ANA production and its more defined clinical utility in lymphoma.

High frequency of ofloxacin resistance patterns of Mycobacterium leprae from India: An indication to revisit second line anti-leprosy treatment regimen.

OBJECTIVES: Drug resistance in leprosy is an emerging concern, leading to treatment failures, recurrences, and potential spread of resistant Mycobacterium leprae in the community. In this study, we aimed to assess drug resistance prevalence and patterns amongst leprosy patients at a tertiary care referral hospital in India. METHODS: Mutations in drug resistance determining regions for dapsone, rifampicin, and ofloxacin of the M. leprae genome in DNA extracted from skin biopsies of 136 leprosy patients (treatment-naive = 67, with persistent skin lesions = 35, with recurrence = 34) were analysed by polymerase chain reaction followed by Sanger sequencing. Wild-type strain (Thai-53) was used as a reference strain. RESULTS: Resistance mutations were identified in a total of 23 patients, constituting 16.9% of the cohort. Within this subset of 23 cases, resistance to ofloxacin was observed in 17 individuals (12.5%), while resistance to both dapsone and rifampicin was detected in three patients each (2.2% for both). The occurrence of ofloxacin resistance showed minimal disparity between recurrent and treatment-naive cases, at 17.6% and 16.4%, respectively. Dapsone resistance emerged in two treatment-naive cases and one case with persistent skin lesions. Notably, none of the treatment-naive cases or those with recurrence/relapse exhibited rifampicin resistance. Subsequently, no statistically significant correlation was identified between other clinical variables and the presence of antimicrobial resistance. CONCLUSIONS: The occurrence of resistance to the current multidrug therapy regimen (specifically dapsone and rifampicin) and to ofloxacin, a secondary antileprosy medication in M. leprae, represents a concerning scenario. This calls for an expansion towards bactericidal drug options and the establishment of robust surveillance for drug resistance in countries burdened with high leprosy rates. Moreover, the introduction of stringent antimicrobial stewardship initiatives is imperative. As a single centre study, it represents a limited, cross-sectional view of the real situation in the field.

Is there any association between cognitive deficits and immune markers in Acute and Transient psychotic disorders? A pilot study.

BACKGROUND: There are studies to support association between immune function and cognition in patients with schizophrenia (SZ). However, there are no such study which had tried to explore the same in patients with Acute and transient psychotic disorders (ATPDs), which is considered to similar in presentation to SZ. METHODS: This is an extended analysis of the study published in which we had recruited 19 subjects with ATPDs in acute phase of illness were age-/gender-matched with patients schizophrenia in remission. Clinical assessment and immune-marker levels (IL-6,IL-8,IL-17) were carried out along with follow -up repeat immune-marker levels assessment in the ATPD group was conducted after remission status was ensured (at least 3 months after resolution of acute phase). Cognitive assessment was done on Montreal Cognitive Assessment Scale (MoCA) in both the groups (ATPD in both phases and in SZ). RESULTS: The mean MoCA total score was 12.05 (SD-5.0) in the acute phase and 27.05 (SD-2.46) in the remission phase in the ATPD group which was statistically significant. When compared with patients with SZ in remission, patients with ATPD in remission performed better in all domains of MoCA, however only statistically significant differences in the total MoCA score and in the visuospatial domain scores of MoCA. No significant association between any of the immune marker levels (IL-6, Il-8 and IL-17) with any domains of the MoCA in patients with ATPD neither in the acute phase nor in the remission phase was found. Additionally, no significant association between the cognitive scores in the MoCA domains of the patients with schizophrenia and immune marker levels was found too. CONCLUSION: To conclude, the present study's findings suggested that there existed definite cognitive deficits in patients with ATPDs in both acute and remission phase and in patients with SZ. However, the study could not establish any relationship/association between cognitive deficits/scores in patients with ATPDs in both phases as well as in patients with SZ with immune marker levels.

Association of HLA-DRB1 alleles with anti-D alloimmunization in RhD negative pregnant women in India.

BACKGROUND: Human leukocyte antigen (HLA) restriction plays an important role in the susceptibility to alloimmunization against red blood cell (RBC) antigens. The prevalence of anti-D alloimmunization in RhD negative pregnancy is still quite high in our population. Thus, we planned this study to determine the association of HLA-DRB1 alleles with anti-D alloimmunization in RhD negative pregnant women. MATERIAL AND METHODS: RBC antibody screen (ABS) was performed for RhD negative pregnant women attending the antenatal clinic our institute. Those with a negative result were included in the 'non-alloimmunized' (NAL) group ('Control' group), while those with anti-D alloantibody on performing antibody identification were included in the alloimmunized (AL) group of the study (n = 50 each). ABS and identification were done using column agglutination technique. The HLA-DRB1 typing was done by Luminex based reverse sequence specific oligonucleotide probing (SSOP) using commercial kits. The HLA-DRB1 allele frequency was compared in both the groups. RESULTS: There was a significant difference between the two groups in terms of gravida (p < 0.001) and history of anti-D immunoprophylaxis (p < 0.001). The frequency of HLA-DRB1*03 and HLA-DRB1*04 alleles was significantly higher in the AL group than the NAL group: 40 % versus 18 % [Odds Ratio (OR): 3.04, 95 % CI: 1.21-7.6; p = 0.015] for HLA-DRB1*03 alleles and 18 % versus 4 % (OR: 5.27, 95 % CI: 1.08-25.78, p = 0.025) for HLA-DRB1*04 alleles. CONCLUSION: The frequency of HLADRB1*03 and HLADRB1*04 alleles was significantly higher in RhD negative pregnant women alloimmunized with anti-D alloantibody.

Circulating "Neutrophils extra-cellular traps" during the early post-renal transplant period and correlation with graft dysfunction and rejection.

BACKGROUND: Neutrophil extracellular traps (NETs) have a role in infection, autoimmunity, autoinflammation, thrombosis, ischemia-reperfusion injury (IRI), epithelial-mesenchymal transition, vasculitis, and metabolic diseases. However, its role in early graft injury and graft outcome has not been elucidated till now. We evaluated the circulating NETs during early post-transplant periods and their correlation with graft outcome and IRI. METHODS: Prospectively, thirty kidney transplants recipient (KTR) were recruited and grouped into non-dysfunction (Group-A) and dysfunction groups (Group-B). Serum levels of circulating NETs were estimated by measuring myeloperoxidase-DNA complex at three-time points: pre-transplant, 8 h post-transplant, and 18 h post-transplant; and correlated with early graft outcome. Malondialdehyde (MDA), a marker of oxidative stress or IRI, was also measured to assess its relation with NETs and early graft outcome. RESULTS: Circulating NETs were significantly increased in both non-dysfunctional [Median OD: 0.11 (0.01-0.19) to 0.51 (0.22-0.91); p = 0.001] and dysfunctional [Median OD: 0.16 (0.12-0.27) to 0.38 (0.19-0.68); p = 0.047] KTR during first 8 h of transplant followed by fall at 18 h post-transplant [0.25 (0.18-0.72) and 0.35 (0.26-0.36) respectively]; however, no significant difference were observed between two groups at any time points. Isolated biopsy-proven graft rejection KTR also had higher circulating NETs during the early post-transplant period [Median OD: 0.16 (0.13-0.31) to 0.38 (0.28-1.5); p > 0.05] but no significant difference compared to non-dysfunctional KTR. MDA also displayed similar trends with an early significant rise [9.30 (7.74-12.56) µM to 17.37 (9.11-22.25) µM; p = 0.03 in group-A, and 8.7 (6.04-10.30) µM to 14.66 (13.39-21.63) µM; p = 0.01in group-B] followed by fall at 18 h in both groups [10.21 (7.64-13.90) µM and 11.11 (9.15-17.54) µM respectively]. Despite similar trends of both NETs and MDA, there was no significant correlation between these; however, creatinine exhibits a significant inverse correlation with NETs and MDA both. CONCLUSION: Circulating NETs are significantly increased during the early post-transplant period in KTR irrespective of early graft outcome. Similar dynamics of MDA indicate that the early rise of NETs might be a part of IRI. However, molecular studies with large sample sizes and longer follow up are required to reach more defined conclusions.

Comparison of Multisystem Inflammatory Syndrome (MIS-C) and Dengue in Hospitalized Children.

OBJECTIVE: Multisystem inflammatory syndrome (MIS-C) in children is a febrile illness that has overlapping presentation with other locally prevalent illnesses. Clinicolaboratory profile of children admitted with MIS-C and dengue were compared to understand their presentation at the outset. METHODS: This was a retrospective study of children ≤ 12 y admitted with MIS-C (WHO definition) or laboratory-confirmed dengue between August 2020 and January 2021 at a tertiary center in North India. RESULTS: A total of 84 children (MIS-C - 40; dengue - 44) were included. The mean (SD) age [83.5 (39) vs. 91.6 (35) mo] was comparable. Rash (72.5% vs. 22.7%), conjunctival injection (60% vs. 2.3%), oral mucocutaneous changes (27.5% vs. 0) and gallop rhythm (15% vs. 0) were seen more frequently with MIS-C, while petechiae [29.5% vs. 7.5%], myalgia (38.6% vs. 10%), headache (22.7% vs. 2.5%), and hepatomegaly (68.2% vs. 27.5%) were more common with dengue. Children with MIS-C had significantly higher C-reactive protein (124 vs. 3.2 mg/L) and interleukin 6 (95.3 vs. 20.7 ng/mL), while those with dengue had higher hemoglobin (12 vs. 10.2 g/dL) lower mean platelet count (26 vs. 140 × 109/L), and greater elevation in aspartate (607 vs. 44 IU/L) and alanine (235.5 vs. 56 IU/L) aminotransferases. The hospital stay was longer with MIS-C; however, PICU stay and mortality were comparable. CONCLUSION: In hospitalized children with acute febrile illness, the presence of mucocutaneous features and highly elevated CRP could distinguish MIS-C from dengue. The presence of petechiae, hepatomegaly, and hemoconcentration may favor a diagnosis of dengue.

Immune-mediated inflammatory markers in acute and transient psychotic disorders-comparison with schizophrenia: An exploratory comparative study.

AIM: Considering Acute and Transient psychotic disorders (ATPDs) to be a close entity to Schizophrenia (SZ) with a completely different course and outcome, studies evaluating the immunological abnormalities are scarce in ATPDs. We analysed immune-mediated inflammatory marker levels [Interleukin-2 (IL-2), Interleukin-4 (IL-4), Interleukin-6 (IL-6), Interleukin-8 (IL-8), Interleukin-17 (IL-17) and Tumour necrosis factor-alpha (TNF-α)] in patients with ATPDs (in the acute phase and after remission), and compared these with patients with SZ in remission and with healthy controls. METHODS: Ninteen subjects with ATPDs in acute phase of illness were age-/gender-matched with healthy controls and patients with schizophrenia in remission; recruited through purposive sampling. Clinical assessment and immune-marker levels were carried out in all the three groups. Follow -up repeat immune-marker levels assessment in the ATPD group was conducted after remission status was ensured. Immune-marker levels were compared across the three groups. RESULTS: Patients with ATPDs had elevated levels of the pro-inflammatory cytokines IL-6 and IL-17 and low levels of IL-8 in the acute phase and low levels of IL-6 and elevated levels of IL-8 during the remission phase. Compared to patients with SZ in remission, patients with ATPD in remission had low levels of all the three pro-inflammatory cytokines (with significantly low IL-6 levels and non-significant, yet low levels of IL-8 and IL-17) and had significantly low and high levels of IL-6 and IL-8 respectively than healthy controls. CONCLUSION: These findings suggest that there existed immunological abnormalities in the acute and remission phase of illness in patients with ATPDs compared to both patients with SZ in remission and healthy controls.

Peripheral nervous system involvement in Sjogren's syndrome and its impact on quality of life.

Sjogren's syndrome (SS) is a multisystem disorder of autoimmune etiology, which can be primary or secondary. Quality of life in SS depends on severity of involvement of different systems. The aims of this study are to analyze peripheral nervous system involvement in primary and secondary SS and its impact on quality of life (QOL). In this cross-sectional observational study conducted between January 2020 and June 2021, 67 patients of SS attending to this tertiary care center were included. Nerve conduction study and sympathetic skin response test were done in all cases. QOL was assessed with SF-36 questionnaire. Out of 67 cases, 50 had primary and 17 had secondary SS. 50.7% of cases had peripheral neuropathy. In primary SS, prevalence of peripheral neuropathy was 56% as against 35.3% in secondary. 50% of peripheral neuropathy were asymptomatic and were diagnosed after electrodiagnostic tests. Polyneuropathy was the most common pattern. There was no difference of other system involvement or immunological markers among those with and without peripheral neuropathy in either primary or secondary SS. Cases with peripheral neuropathy in the primary Sjogren's group and in the cohort as a whole scored significantly lower in 7 domains of SF-36. Peripheral nervous system involvement is common in Sjogren's syndrome, and most of them are asymptomatic. Peripheral neuropathy has significant impact on QOL in people with SS. Early detection and halting the progression of asymptomatic cases can be helpful in improving QOL.

Anti-staphylococcal responses and their relationship with HLA-DR-DQ polymorphism in granulomatosis with polyangiitis: a preliminary evidence of association with disease outcome.

Chronic nasal carriage of Staphylococcus aureus (S. aureus) is a risk factor for relapse of granulomatosis with polyangiitis (GPA), and genetic susceptibility to infections and autoimmune diseases is majorly affected by HLA genes. Previous studies have shown the association of HLA Class-II genes with GPA susceptibility. Here, we aim to assess immune responses of GPA patients against S. aureus antigens in relation to the HLA-DR-DQ genes polymorphism to determine the disease outcome. A total of 45 GPA patients and 128 healthy controls during 2010-2012 were included in this case-control study. HLA-DRB1/DQB1 allele typing was performed by polymerase chain reaction-sequence-specific primer (PCR-SSP) method. Immune responses against S. aureus antigens were investigated in 20 active vs. remitting GPA (after 6 months of cyclophosphamide and glucocorticoids) patients by Western blot. Statistical analysis was performed using χ2 test and Fisher's exact test. We observed a significant association of DRB1*08, DRB1*16 and DQB1*04 alleles with GPA susceptibility, whereas DRB1*15, DRB1*10 and DQB1*05 alleles were suggested as protective alleles. Among S. aureus antigens, active GPA patients' sera reacted more strongly with 34 and 24 kDa antigens of S. aureus than remitting and healthy control  sera. Furthermore, we observed that the lack of DQB1*06 allele confers complete remission even in the presence of anti-S. aureus antibodies against 24 kDa protein. Our findings suggest that the presence of DQB1*06 allele and S. aureus infection may prolong active disease. Further, our study indicates the potential of using anti-staphylococcal medications for achieving remission in patients having HLA-DQB1*06 allele.

Bullous pemphigoid in India: Review of cases registered in an autoimmune bullous disease clinic.

Background Information on bullous pemphigoid in an Indian context is scarce. Aim To report clinico-demographic profile, associated comorbidities and prescription pattern of bullous pemphigoid patients in India. Methods This was a retrospective study, where past records of all bullous pemphigoid patients diagnosed and treated between November 2013 and October 2019 were accessed and analysed. Patients having a compatible clinical presentation with either histopathological and/or direct immunofluorescence evidence of bullous pemphigoid were included. Results There were 96 bullous pemphigoid patients, with a male: female ratio of 1.6:1. The mean age at diagnosis was 62.5 ± 2.2 years, with mean duration of illness 27.5 ± 4.5 months before presentation. Comorbidities were present in 80 (83%) patients, with type 2 diabetes mellitus (38.5%), hypertension (36.4%) and neurological illness (16.7%) being the commonest ones. Clinically, blisters were the predominant presentation in 81 (84.4%) patients. The majority (87.5%) of patients showed a predominant eosinophilic infiltrate on histopathology. Direct immunofluorescence revealed immunoglobulin G deposits with complement C3 in 77 (80.2%) cases. The majority of patients (77.1%) were treated with oral prednisolone, either alone (11.5%) or in combination (65.6%) with other topical and systemic agents. Topical steroids were used in 29.1%, azathioprine in 28%, dapsone in 16.7% and omalizumab in 6.2% of patients. Limitations The study is retrospective. Immunofluorescence on salt split skin, direct immunofluorescence serration pattern analysis, and immunoblotting were not performed. Hence, there is a possibility that a few included cases were suffering from other subepidermal autoimmune bullous diseases like epidermolysis bullosa acquisita or anti-p200 pemphigoid. Conclusion Bullous pemphigoid patients in this study had a younger age of onset and showed male preponderance. Comorbidities like type 2 diabetes, hypertension and neurological disorders were frequent. Cutaneous blisters were the most frequent clinical presentation. Systemic corticosteroids comprised the mainstay of therapy.

Comparative evaluation of interleukin-10, transforming growth factor-ß, and interleukin-17 in gastrointestinal tuberculosis and crohn's disease.

Background: Gastrointestinal tuberculosis (GITB) and Crohn's disease (CD) are close mimickers and difficult to discriminate. Recent work has focused on the immunological differences between GITB and CD based on cytokines related to T-regulatory cells and Th17 cells. In the present cross-sectional study, suspected cases of GITB or CD underwent extensive clinical, radiological, endoscopic, histological, and microbiological assessment. The diagnosis was based on standard criteria and response to antitubercular therapy endoscopically. Methods: Interleukin (IL)-10, transforming growth factor-ß (TGF-ß), and IL-17 were measured and compared between GITB and CD along with other parameters. Fisher's exact test and Mann-Whitney U test were used as per the data type. Results: Of the 27 patients, 11 had CD, 9 had GITB, and 7 had other conditions. Chronic diarrhea, involvement of left and long segments of the colon, and aphthous ulcers were significantly more frequent in CD; however, transverse ulcers were in GITB. IL-10 was reduced in both GITB (median-interquartile range [IQR] 9.54 [3.65-24.04]) and CD (median-IQR 13.28 [6.91-22.50]) compared to control (median-IQR 26.72 [10.34-35.43]). TGF-ß showed little variation, but IL-17 was below the detection limit in most cases. None of these cytokines were significantly different between CD and GITB. The sensitivity and specificity of multiplex Mycobacterium tuberculosis-polymerase chain reaction were 44.44% and 100%, respectively. Conclusion: Serum cytokine profiling (IL-10, IL-17, and TGF-ß) could not significantly differentiate GITB and CD. Moreover, extensive molecular, transcriptomic, chemokines, and cytokine analyses may shed light on these aspects.

Managing ANCA-associated vasculitis during COVID-19 pandemic: a single-center cross-sectional study.

The objective of the study is to report the outcomes of COVID-19 in ANCA-associated vasculitis (AAV) patients. This was a registry-based observational study conducted at a tertiary care center in north India. AAV patients with at least one follow-up visit between March 2020 and September 2021 were included. Demographic features, clinical manifestations, disease activity, and treatment details of underlying AAV were noted in all patients. Details of COVID-19 infection including severity, treatment, and outcomes were noted. Predictors of COVID-19 severity were determined using univariate analysis. A total of 33 (18.3%) out of 180 AAV patients contracted COVID-19 infection. Moderate COVID-19 infection was seen in 33.3% and severe or critical infection was seen in 36.3% of patients. Seventeen patients (51.5%) required supplemental oxygen therapy. Nine patients had active disease at the time of COVID-19 infection and three of them died due to COVID-19 infection. The risk of COVID-19 infection and its severity did not differ between patients receiving different immunosuppressants including rituximab induction. Hypothyroidism (p = 0.046) and ocular (p = 0.038) involvement due to AAV predicted the development of moderate to severe/critical COVID-19. Three (9.1%) patients died from COVID-19 and the rate of AAV flare after COVID-19 was similar to that in non-COVID-19 patients (15.3/100 person-year vs. 15.6/100 person-year, p = 0.95). Majority of the patients with AAV had moderate to severe or critical COVID-19 infection. The rate of death due to COVID-19 in AAV is higher than in general population. Use of standard remission induction regimens did not lead to increased risk of COVID-19 infection in our AAV cohort.

Murine cytomegalovirus promotes renal allograft inflammation via Th1/17 cells and IL-17A.

Human cytomegalovirus (HCMV) infection is associated with renal allograft failure. Allograft damage in animal models is accelerated by CMV-induced T helper 17 (Th17) cell infiltrates. However, the mechanisms whereby CMV promotes Th17 cell-mediated pathological organ inflammation are uncharacterized. Here we demonstrate that murine CMV (MCMV)-induced intragraft Th17 cells have a Th1/17 phenotype co-expressing IFN-γ and/or TNF-α, but only a minority of these cells are MCMV specific. Instead, MCMV promotes intragraft expression of CCL20 and CXCL10, which are associated with recruitment of CCR6+ CXCR3+ Th17 cells. MCMV also enhances Th17 cell infiltrates after ischemia-reperfusion injury, independent of allogeneic responses. Pharmacologic inhibition of the Th17 cell signature cytokine, IL-17A, ameliorates MCMV-associated allograft damage without increasing intragraft viral loads or reducing MCMV-specific Th1 cell infiltrates. Clinically, HCMV DNAemia is associated with higher serum IL-17A among renal transplant patients with acute rejection, linking HCMV reactivation with Th17 cell cytokine expression. In summary, CMV promotes allograft damage via cytokine-mediated Th1/17 cell recruitment, which may be pharmacologically targeted to mitigate graft injury while preserving antiviral T cell immunity.

Association of Human Leucocyte Antigen Class II, with viral load and immune response to Epstein-Barr virus in adult and pediatric Systemic lupus erythematosus patients.

OBJECTIVE: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease, which is known to be associated with HLA-DRB1 and Epstein-Barr virus (EBV) infection. In the Indian subcontinent where there is high seroendemicity of EBV, we postulated that the association of this virus in adult SLE (aSLE) and pediatric SLE (pSLE) patients would be different and differentially associate with the HLA-DRB1 susceptibility and protective genes. METHODS: A total of 109 aSLE, 52 pSLE, 215 adult healthy and 63 pediatric healthy controls were recruited. HLA-DRB1 genotyping by PCR-SSP, EBV load estimation by real-time PCR and antibody profiling (IgG & IgM) to EBV antigens by line blot assay were performed. RESULTS: DRB1*15 was found predominant in pSLE patients and DRB1*03 in aSLE patients. DRB1*15/X heterozygous was predominant in overall SLE patients, although disease severity, like hypocomplementemia, higher autoantibody levels and more organ involvement was observed in *15/*15 homozygous state. EBV strongly associated with pSLE patients showing higher percent of EA-D IgG (p < 0.0001) and p22 IgG (p = 0.035) along with higher viral load (p = 0.001) as compared to healthy controls. In addition, the higher EBV DNA load significantly associated with anti-EA-D IgG (p = 0.013) and DRB1*15/*15 (p = 0.007) in pSLE patients as compared to aSLE patients. CONCLUSIONS: This study therefore indicates that different HLA-DRB1 allotypes confer susceptibility to SLE in children and adults and disease may be triggered by increased EBV reactivation.

Antinuclear antibody pattern and autoantibody profiling of systemic sclerosis patients in a tertiary referral center in North India.

Antinuclear antibody (ANA) pattern and autoantibody (autoAb) profiling of 150 adult systemic sclerosis (SSc) patients concerning their clinical association and diagnostic significance were analyzed by indirect immunofluorescence (IIF), immunoblot, and fluorescence enzyme immunoassay. One hundred and forty-three (95.3%) patients had positive ANA: DNA topoisomerase I (topo I)-like pattern-84(56%); speckled pattern-44(29.3%);centromere pattern-7(4.6%); and nucleolar pattern-4(2.6%). Three distinct topo I-like immunofluorescence patterns were detected at 1:40 dilution. Topo I-like pattern (32/75-limited cutaneous systemic sclerosis (lcSSc) vs. 52/75-diffuse cutaneous systemic sclerosis (dcSSc); p < 0.001) was found to be associated with dcSSc subset and speckled pattern (lcSSc 28/75 vs. dcSSc 16/75; p < 0.03) with lcSSc subset. One hundred and thirty-eight (92%) patients were positive for SSc-associated autoAbs. The frequency distribution of autoAbs to topo I, centromere A (CENP A) and centromereB (CENP B), RNA polymerase III (RP11, RP155), fibrillarin (U3RNP), nucleolus organizer region (NOR)-90, Th/To, PM-Scl75, PM-Scl100, Ku, platelet-derived growth factor receptor (PDGFR) and Ro-52, were 87(58%), 9(6%), 8(5.3%), 6(4%), 9(6%), 0, 6(4%), 6(4%), 8(5.3%), 5(3.3%), 11(7.3%),0 and 46(30.6%), respectively. Topo I autoAb was strongly associated with dcSSc (35/75 lcSSc vs. 52/75 dcSSc; p < 0.004), Raynaud's (p < 0.003), interstitial lung disease (ILD) (p < 0.001) and pulmonary arterial hypertension (PAH) (p < 0.04). This study helps in defining SSc clinical subset, prognostic markers of disease severity, characterization of the topo I-like ANA pattern, and provides a definite association between the ANA patterns and corresponding autoAb.

Increased gene expression of B cell-activating factor of tumor necrosis factor family, in remitting antineutrophil cytoplasmic antibody-associated vasculitis patients.

AIM: To study the expression of B cell-activating factor of tumor necrosis factor family (BAFF) and A proliferation-inducing ligand (APRIL) genes in active and remitting patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) and healthy controls and their correlation with disease activity. METHODS: This was a prospective case-control study. Gene expressions of BAFF and APRIL were studied in 32 patients with AAV (16 each with active disease and in remission) and 30 healthy age and sex matched controls by real-time polymerase chain reaction. RESULTS: Out of 32 AAV patients, 26 had granulomatosis with polyangiitis (GPA) and 6 had microscopic polyangiitis (MPA). Mean ages of patients in active (12 GPA and 4 MPA) and remission (14 GPA and 2 MPA) groups were 39.4 ± 17.2 and 44.6 ± 16.1 years, respectively. BAFF gene expression was significantly higher in both the active AAV group and remission AAV group compared to controls (P < .01). The BAFF expression was significantly higher in AAV patients in remission compared to active AAV patients (P = .003). In contrast, APRIL expression did not differ between AAV patients and controls (P = .829). However, APRIL had significantly higher expression in remission as compared to active patients (P = .048). There was no significant correlation of both BAFF and APRIL expression with disease activity markers (erythrocyte sedimentation rate, C-reactive protein, platelets and Birmingham Vasculitis Activity Score version 3). CONCLUSION: BAFF gene is significantly expressed in patients with AAV. Among AAV patients, there is a significantly higher expression of BAFF and APRIL in remitting state of the disease as compared to active state. There is no significant change in APRIL gene expression in patients with AAV as compared to controls. This makes a case for anti-BAFF therapy in future for AAV patients in northern India.

Association of immunological features with clinical manifestations in primary Sjogren's syndrome: a single-center cross-sectional study.

The objectives of this study were to describe the clinical features and evaluate the utility of immunological features as predictors of organ involvement and disease severity in patients with primary Sjogren's syndrome (pSS). In this single-center observational cross-sectional study, subjects fulfilling the 2012 AECG criteria or 2016 ACR/EULAR criteria for pSS were included. Details of glandular, extra-glandular manifestations, ESSDAI, ESSPRI, ANA, anti-Ro/La antibodies, rheumatoid factor (RF), complement (C3 and C4) levels and hyperglobulinemia were noted. Chi-square and Mann-Whitney U tests were performed for determining associations and relative risk (RR) was calculated. Sixty-four subjects with pSS were included in the study. Females constituted 92% and median age at onset was 37.5 (15-74) years. Ocular or oral sicca was noted in 61 (95.3%) subjects and parotidomegaly was noted in 17 (26.5%) subjects. Extra-glandular manifestations noted were: constitutional (85.9%), articular (65.6%), renal (29.6%), hematological (26.6%), cutaneous (12.5%), peripheral nerves (9.3%) and pulmonary (4.7%). Immunological features noted were: ANA (85.9%), anti-Ro (81.3%), anti-La (60.9%), RF (84.4%), hypocomplementemia (39.1%) and hyperglobulinemia (62.5%). Median ESSDAI was 6 (0-23) and ESSPRI was 7 (0-10). ANA was associated with younger age and renal involvement (RR 1.25). Anti-Ro was associated with younger age, renal involvement (RR 1.36) and high ESSDAI. Anti-La was associated with high renal (RR 3.4) and low articular involvement (RR 2.75). RF was associated with hematological involvement and hyperglobulinemia was associated with younger age. Certain immunological features can help predict the organ involvement in patients with pSS. Larger, prospective follow-up studies are needed to clearly understand these associations.