Mannose Binding Lectin Levels and its Association with Systemic Lupus Erythematosus Disease Severity: An Indian Report

Background: Inflammatory response in COVID-19 responsible for acute respiratory distress syndrome (ARDS) and multiorgan failure and play a major role in morbidity and mortality of patients. The present study was undertaken to assess serum level of cytokines and its association with other inflammatory markers and disease severity in COVID-19 and hence their prognostic significance. Methods: This was a retrospective observational study of 175 admitted COVID-19 patients. The patient’s clinical data, laboratory investigations, inflammatory markers and serum level of cytokines [interleukin-1? (IL-1?), interleukin-6 (IL-6), interleukin-10 (IL-10) and tumour necrosis factor ? (TNF?)] were extracted from their medical records. All patients were divided into three groups viz. group A had asymptomatic patients, group B had mild to moderate ill patients and group C had severe or critical ill patients. Above parameters were analysed and comparative evaluation with severity of disease was done. Results: In present study 55% patients were asymptomatic, 24% patients were mild to moderate illness and remaining 21% patients had severe or critical illness. Fever, cough, dyspnoea and co-morbidities including hypertension and diabetes were more common in group C. Absolute lymphocyte count (ALC), lymphocyte- monocyte ratio (LMR) showed decreasing trend whereas absolute neutrophil count (ANC), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and eosinophil-lymphocyte (ELR) showed increasing trend with increase in disease severity. Serum IL-6 was found to be significantly higher in group C (64.98±111.18pg/mL) as compared to group B (15.51±20.66pg/mL) and group A (5.04±56.1pg/mL) (P<0.001). Receiver operating characteristic (ROC) curve for IL-6 to differentiate the patients with severe disease from asymptomatic and mild symptomatic disease showed a cut-off of 6.75pg/ml. Conclusion: Elevated IL-6 levels lead to adverse clinical events so IL-6 level might serve as a potential prognostic marker for severity of disease in COVID-19. Inhibition of IL-6 might be helpful to prevent serious adverse events in COVID-19 infection.

Mannose binding lectin (MBL) 2 gene polymorphism & its association with clinical manifestations in systemic lupus erythematosus (SLE) patients from western India.

Background & objectives: systemic lupus erythematosus (SLE) is a prototypical autoimmune disease characterized by production of autoantibodies. Mannose binding lectin (MBL) is an important element of the innate defense system. the present study was undertaken to determine whether variant alleles in MBL2 gene were associated with disease severity in SLE patients. Methods: The MBL alleles [-550, -221, +4, Codon 52, Codon 54 and Codon 57] were studied by PCR- RFLP (restriction fragment length polymorphism) method in 100 SLE patients fulfilling ACR (American College of Rheumatology) criteria along with 100 healthy controls. SLE disease activity was evaluated using SLE Disease Activity Index (SLEDAI) score. Results: Homozygosity for MBL variant allele (O/O) was observed in 24 per cent of the SLE patients compared to 16 per cent of the normal controls, while no difference was found for heterozygosity (A/O) (37 vs 35%). A significant difference was reported in incidence of double heterozygosity for mutant allele B and D (B/D) among SLE patients as against control group (p = 0.015). MBL genotypes did not show any association with renal involvement. Interpretation & conclusions: In this study from western India, MBL gene polymorphism showed an influence as a possible risk factor for susceptibility to SLE, but had no direct effect on disease characteristics. Further studies need to be done on a larger number of SLE patients in different regions of the country.

Toll-like receptors in autoimmunity with special reference to systemic lupus erythematosus.

The Toll-like receptor (TLR) family plays a fundamental role in host innate immunity by mounting a rapid and potent inflammatory response to pathogen infection. TLRs recognize distinct microbial components and activate intracellular signaling pathways that induce expression of host inflammatory genes. Several studies have indicated that TLRs are implicated in many inflammatory and immune disorders. Extensive research in the past decade to understand TLR-mediated mechanisms of innate immunity has enabled pharmaceutical companies to begin to develop novel therapeutics for the purpose of controlling an inflammatory disease. The roles of TLRs in the development of autoimmune diseases have been studied. TLR7 and TLR9 have key roles in production of autoantibodies and/or in development of systemic autoimmune disease. It remains to be determined their role in apoptosis, in the pathogenesis of RNA containing immune complexes, differential expression of TLRs by T regulatory cells.