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The lectin pathway of complement aids in removing apoptotic cells and maintenance of tissue homeostasis. However, its role in SLE pathogenesis remains unknown. This study aimed to assess the association of ficolins, mannose-binding lectin (MBL), and other pathogen recognition molecules (PRMs) of the lectin pathway and their corresponding autoantibodies with various clinical manifestations and disease activity in SLE patients from Western India. In this cross-sectional study, 282 clinically diagnosed SLE patients were included. Serum levels of ficolins, antigenic MBL, MBL-associated serine proteases (MASPs), MBL-associated protein 44 (MAp44), Collectin liver-1 (CL-L1), and their corresponding autoantibodies were quantified using ELISA. Group differences were analyzed using Mann-Whitney U tests, while associations/relationships were evaluated using chi-square tests and Spearman’s correlations. Serum levels of ficolin-2 ( p < 0.001 ), MASP-3 ( p = 0.030 ), and MAp44 ( p < 0.001 ) were significantly elevated, while antigenic MBL ( p < 0.001 ) and MASP-1 ( p < 0.001 ) were significantly reduced in SLE patients compared to healthy controls (HCs). Renal involvement was associated with elevated ficolin-1 ( p = 0.009 ), while hematological manifestations were linked to reduced MASP-1 ( p = 0.018 ), MASP-3 ( p = 0.002 ), and MAp44 ( p = 0.002 ) levels. Mucocutaneous manifestations were associated with elevated MAp44 ( p < 0.001 ) and anti-ficolin-1 ( p = 0.038 ) autoantibodies. Anti-ficolin-1 ( p = 0.001 ), anti-ficolin-2 ( p = 0.001 ), and anti-ficolin-3 ( p < 0.001 ) autoantibodies were significantly elevated in SLE patients compared to HCs. Anti-ficolin-2 autoantibodies were negatively correlated with ficolin-2 ( r =-0.153, p  = 0.015). Anti-MBL antibodies were correlated with SLEDAI ( r  = 0.169, p  = 0.007) and anti-dsDNA antibodies ( r  = 0.178, p  = 0.005). These findings indicate altered levels of lectin pathway-associated PRMs and their corresponding autoantibodies in SLE. Their association with clinical manifestations, disease activity, and complement-related parameters, suggest their potential as novel biomarkers in SLE.

Interferon(IFN) system is dysregulated in Systemic Lupus Erythematosus(SLE) and represents potential therapeutic target. However, most studies have focused on isolated IFN types, particularly type I and type II, while type III IFNs remain poorly characterized. Comprehensive analysis of different IFN types in parallel with interferon-stimulated gene(ISG) expression is limited despite the interconnectedness of IFN families and their potential to differentially influence disease activity, immune phenotypes, and treatment responses. The present study assessed levels of IFN types and IFN score to evaluate their association with disease activity, clinical manifestations, and autoantibody profile in SLE patients from Western India. This cross-sectional study included clinically diagnosed SLE patients(n=115). Serum IFNα and IFNλ1-λ4 levels were detected using ELISA, while IFNγ levels were detected using bead-based assay, and IFN score by RT-qPCR based on the expression of five ISGs. SLE patients with IFN levels above third quartile were categorized as 'IFN high' groups, and their association with clinical and autoantibody profile were analysed using logistic regression. To identify patient subgroups based on autoantibody profile, unsupervised clustering was employed. SLE patients showed significantly elevated IFNα(p<0.001), IFNγ(p=0.009), and IFNλ3(p<0.001) levels as well as IFN score(p<0.001) as compared to healthy controls. IFN score(r=0.228;p=0.014) and IFNα levels(r=0.430;p<0.001) correlated positively with disease activity. IFNα high group was associated with leukopenia (OR(95%CI):5.81(1.29,26.20);p=0.022) and multiple autoantibodies, while IFNγ high group with rash (OR(95%CI):2.73(1.06,7.00);p=0.037). FNλ3 high group showed positive association with anti-Ro52 autoantibodies (OR(95%CI):2.64(1.07,6.52);p=0.035) and negative association with low complement (OR(95%CI):0.35(0.13,0.89);p=0.028). IFNλ4 levels were not significantly elevated in SLE patients(p=0.642), however the levels were significantly associated with IFN score(r=0.359,p<0.001) and anti-dsDNA positivity(r=0.323,p<0.001), with higher levels observed in IFN score high SLE patients(p=0.016). Autoantibody profile-based clustering identified three subgroups differing in IFNα levels, IFN scores, disease activity, and associated immunological parameters. All three IFN pathways were elevated in SLE. Correlation of IFNα levels and IFN score with SLEDAI suggested their potential as possible biomarker for monitoring disease activity. Association of IFNλ4 with IFN score suggested their possible role in IFN pathway activation.By assessing IFNs at both protein and transcriptional levels, present study provided comprehensive insight into IFN pathway dynamics and IFN-driven heterogeneity in SLE.

Connective tissue disease-associated interstitial lung disease (CTD-ILD) is a major cause of morbidity and mortality in autoimmune disorders, yet detailed serological characterization remains limited in Indian cohorts. This study aimed to evaluate and compare demographic, radiological, autoantibody, and serum profiles between CTD-ILD and non-CTD-ILD patients from Western India and to delineate hospitalization patterns and mortality outcomes among CTD-ILD patients. This single-centre, cross-sectional study enrolled 200 patients with ILD (  = 90 with CTD-ILD and  = 110 with non-CTD-ILD) from a tertiary care centre who were evaluated on a clinico-radiological basis. Antinuclear antibodies and ANA subspecificities were assessed using indirect immunofluorescence and a line blot assay. Serological parameters were quantified using ELISA and multiplex bead-based assays. CTD-ILD patients were significantly younger (49 vs. 57 years;  < 0.001) and predominantly female (80.0% vs. 59.1%;  = 0.002). NSIP predominated in CTD-ILD (51.1%), whereas UIP predominated in non-CTD-ILD (46.4%;  < 0.001). On multivariable analysis, younger age (aOR = 0.954;  < 0.001), female sex (aOR = 2.709;  = 0.023), NSIP (aOR = 6.155;  = 0.001), and UIP (aOR = 8.877;  < 0.001) were independent predictors of CTD-ILD. ANA positivity was higher in CTD-ILD (70.0% vs. 54.5%;  = 0.025), with a predominance of high-titre ANA (81.0%, ≥1:160) and a speckled IFA pattern. The nucleolar pattern was significantly more prevalent in the CTD-ILD group (11.1%;  = 0.010). Disease-specific autoantibody enrichment was observed as follows: anti-SSA/Ro and AMA-M2 in RA-ILD, anti-RNP/Sm in MCTD-ILD, and anti-Scl-70 in SSc-ILD. Anti-MDA5 (  = 0.001), LDH (  = 0.019), and pro-inflammatory cytokines TNF-α, IFN-γ, IL-4, and IL-22 were significantly elevated in CTD-ILD, whereas MMP7 levels were lower (  = 0.025). TNF-α, IL-22, and IL-4 remained independent predictors in the multivariable analysis. Among CTD-ILD patients, 20.0% required hospitalization, with significantly higher in-hospital mortality in admitted patients (27.8% vs. 4.2%;  = 0.007) than in non-admitted CTD-ILD patients. CTD-ILD patients demonstrated distinct demographic, radiological, autoantibody, and serological profiles compared to non-CTD-ILD patients, characterized by elevated anti-MDA5, LDH, and pro-inflammatory cytokines alongside lower MMP7 levels, reflecting an immune-driven rather than fibrosis-dominant pathobiology. These findings contribute to bridging the knowledge gap in the serological characterization of CTD-ILD in Indian cohorts.

Context: Myofibroblasts are fibroblasts with smooth muscle-like features characterized by the presence of a contractile apparatus and found in the connective tissue stroma of normal tissues such as blood vessels and lymph nodes. They are now thought to play a role in the synthesis and reorganization of extracellular matrix, which could contribute to the aggressive biologic behavior of the lesions. Aims: To compare the mean number of stromal myofibroblasts in dentigerous cysts (DCs), keratocystic odontogenic tumor (KCOT) and ameloblastoma; and to derive a correlation between the stromal myofibroblasts and the known biologic behavior of the lesions. Settings and Design: A cross-sectional immunohistochemical analysis of cases of DC, KCOT and ameloblastoma. Materials and Methods: Twenty paraffin-embedded tissue blocks each of DC, KCOT and multicystic ameloblastoma were selected for the study and diagnosis confirmed through hematoxylin and eosin staining. Tissue sections were analyzed for the number of myofibroblasts using alpha smooth muscle actin (α-SMA) immunostaining. Statistical Analysis: Differences in the mean number of α-SMA positive cells in each group were analyzed using one-way ANOVA test. Intergroup comparisons of mean values of α-SMA positive cells were performed using Mann-Whitney U-test. Results: Ameloblastoma showed the highest number of myofibroblasts, whereas DC showed the lowest. Among the groups, there were significant differences between the myofibroblast counts among DC and KCOT and between DC and ameloblastoma, whereas the difference in counts was not statistically significant between KCOT and ameloblastoma. A positive correlation was observed between the myofibroblast count and the known biologic behavior of the lesions. Conclusion: Myofibroblasts may act in close association with the epithelial cells to bring about changes in stromal microenvironment, favorable to the growth and progression of the lesion. They may be of great value in predicting the biologic behavior and growth potential of such lesions.

Purpose Wiskott-Aldrich syndrome (WAS) is an X-linked genetic disorder characterized by distinctive features including microthrombocytopenia, eczema and recurrent infections. In the present study we report clinical, immunological and molecular spectrum of 41 WAS patients diagnosed over last five years. Methods Clinical and family history was collected from case records. Comprehensive immunological assessments including lymphocyte subset analysis, and flow cytometry based evaluation of WAS protein (WASP) expressions were performed in patients along with evaluation of carrier status in mothers. Genetic analysis was carried out with either Sanger sequencing or targeted exome sequencing. Results The patients included in this study presented at a median age of 9.5 months, with two adult cases. Clinical manifestations encompassed thrombocytopenia, eczema, bleeding, diarrhea, respiratory tract infections, CMV infection, and malignancy. Immunological phenotype revealed T cell lymphopenia, B cell lymphopenia, and elevated IgE levels. Flow cytometry analysis of WASP was performed in 36 cases out of which 68.42% demonstrated complete absent expression while others showed reduced expression. Genetic analysis highlighted that the majority of mutations affect the WH1 domain of WASP while both adult patients showed intronic mutations. Molecular Dynamics analysis conducted for the novel variants P398R and G33R showed an average RMSD (Å) higher than that of the wild type, indicating greater structural perturbations in WASP. Conclusion In the present study we have documented 56.09% novel WAS mutations in Indian cohort. Notably, the application of flow cytometry has emerged as a valuable and efficient diagnostic tool for identifying these WAS patients.

Yoga-based clinical research has shown considerable promise in varied ageing-related health outcomes in older adults. However, robust frameworks have yet to be used in intervention research to endorse yoga as a healthy ageing intervention to test the multidimensional construct of healthy ageing. This was an assessor-masked, randomized controlled trial conducted among 258 sedentary, community-dwelling older adults aged 60–80 years, randomly allocated to 26-week yoga-based intervention (YBI) ( n  = 132) or waitlist control (WLC) ( n  = 126). The effectiveness of YBI was assessed through two separate global statistical tests, generalized estimating equations and rank sum-based test, against a comprehensive healthy aging panel comprised of ten markers representing the domains of physiological and metabolic, cognitive, physical capability, psychological, and social well-being. The secondary outcomes were individual primary marker scores, Klotho, inflammatory markers, and auxiliary blood markers. We could establish the healthy aging effect of the 26-week YBI over WLC using two models of global statistical test (GEE, β  = 0.29; 95% CI = 0.20 to 0.38, p  < 0.001), and rank sum-based test ( β  = 0.28, 95% CI = 0.19 to 0.36, p  < 0.001). There were also significant improvements in direction of benefit at individual levels of all the aging markers. Exploratory evaluation with adopted indices from contemporary clinical trials also validated the potential of YBI for healthy aging; HATICE adapted composite score (mean difference =  − 0.18; 95% CI =  − 0.26 to − 0.09, p  < 0.001) and healthy ageing index (mean difference =  − 0.33; 95% CI =  − 0.63 to − 0.02, p  = 0.03). The global effect of YBI across multiple ageing-related outcomes provides a proof of concept for further large-scale validation. The findings hold a great translational value given the accelerated pace of population aging across the globe. Trial registration: CTRI/2021/02/031373.

Common Variable Immunodeficiency (CVID) is a heterogeneous disorder characterized by impaired antibody production and recurrent infections. In this study we investigated the clinical and immunological features of CVID in Indian patients and develops a machine learning model for predicting disease severity. We retrospectively analyzed 150 patients diagnosed with CVID over a decade at a tertiary care center in India. The median age of diagnosis was 18 years, with a male predominance (62%). The majority of patients (66.6%) had a severe phenotype, with recurrent respiratory tract infections being the most common clinical manifestation (84.2%). Gastrointestinal complications were observed in 45% of patients, while autoimmune manifestations were seen in 21%. All patients exhibited hypogammaglobulinemia. IgA levels varied, with 7.8% normal and 14.5% undetectable. IgM levels were decreased in 85.5% of patients. B-cell analysis revealed 64.4% had reduced class-switched memory B cells, with 21.7% showing very low levels. Nine adult patients presented with late-onset combined immunodeficiency. Genetic testing, performed on 52 patients, identified underlying monogenic causes in 29 pediatric and 15 adult patients. LRBA deficiency was the most common genetic defect, found in seven pediatric and three adult patients. We developed a novel machine learning-based severity prediction model for CVID patients, utilizing readily available lymphocyte subsets, class-switched memory B cell counts, and serum immunoglobulin levels to provide an accessible and robust tool for predicting disease severity using Ameratunga’s clinical severity score. Random Forest outperformed other models across all metrics, achieving an accuracy of 0.853 (95% CI: 0.840–0.866). Feature importance analysis across all models identified Th-Tc ratio, CD19, and IgM levels as the most influential predictors for severity prediction. Our study highlights the diverse clinical and immunological features of CVID in Indian patients, emphasizing the need for early diagnosis and individualized management strategies. The machine learning model developed using commonly available immune parameters provide a robust tool for predicting disease severity, potentially guiding treatment strategies to improve patient outcomes.

The setting up of the Tribal Resettlement and Development Mission was a landmark event in the annals of Adivasi land struggles in Kerala. Although the mission has been successful in providing land to a large number of Adivasi families, it has failed to cater to all the land-related needs of these families, ranging from livelihood to preservation of cultural identity. A field study exposes such issues and advocates the need for a broader interpretation of \"land\" in policymaking.

Abstract Ficolins, encoded by FCN genes, are key pattern recognition molecules of the lectin complement pathway involved in immune complex clearance, a process often impaired in systemic lupus erythematosus (SLE). Genetic polymorphisms in FCN genes may influence disease susceptibility. However, their functional significance in SLE remains unclear. The present study aimed to investigate the association of selected FCN gene single-nucleotide polymorphisms (SNPs) with SLE, lupus nephritis (LN), and serum ficolin levels in a Western Indian cohort. Seven SNPs in FCN1 (rs2989727, rs1071583), FCN2 (rs7851696, rs17549193, rs7865453, rs17514136), and FCN3 (rs3813800) were genotyped in 200 SLE patients and 200 healthy controls using polymerase chain reaction (PCR) sequence-specific primer and PCR restriction fragment length polymorphism. Serum ficolin-1, -2, and -3 levels were measured using ELISA. Statistical analysis included χ2 test, Kruskal–Wallis test, and logistic regression to assess associations and calculate odds ratios with 95% confidence intervals. The analysis identified significant associations of FCN2 rs7851696, rs7865453, and rs17514136, as well as FCN3 rs3813800, with SLE susceptibility. Among LN patients, FCN1 rs2989727 and rs1071583, FCN2 rs17514136, and FCN3 rs3813800 showed significant associations. FCN3 rs3813800 was significantly associated with ficolin-3 levels, while FCN2 rs7865453 was associated with complement component 1q–circulation immune complex levels. These findings provide novel insight into associations of FCN gene polymorphisms with SLE and LN susceptibility, with genotype–phenotype correlations suggesting their biological relevance. Future longitudinal and mechanistic studies are warranted to validate these associations and explore their therapeutic potential.

Cyclotrisilenes can pursue four types of reaction pathways with unsaturated substrates: π -addition, σ -insertion, exocyclic σ -insertion, and ring-opening reactions. A computational investigation of all these reaction pathways of 1,2,3,3-tetramethyl cyclotrisilene c-Si 3 Me 4 ( I ) and 1,2-bis(trimethylsilyl)-3,3-dimethyl cyclotrisilene c-Si 3 Me 2 (SiMe 3 ) 2 ( II ) with phenylacetylene ( R1 ) and benzaldehyde ( R2 ) is carried out. The reaction pathways are found to be significantly influenced by the substituents attached to the cyclotrisilene ring. Both the π -addition and the σ -insertion reactions proceed with moderate activation energy and high exoergicity, and the electronic nature of the functional group is crucial in deciding the favorable pathway. The exocyclic σ -insertion reactions are found to possess a huge energy barrier, irrespective of the steric and electronic nature of cyclotrisilenes and the substrates. While the course of the reaction and the viability of the ring-opening reaction with phenylacetylene are impacted by the nature of cyclotrisilene, the ring-opening reactions of I and II with benzaldehyde are both highly endoergic.