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Mannose-binding lectin (MBL) codon 54 (rs1800450) polymorphism predisposes towards medium vessel vasculitis in patients with systemic lupus erythematosus

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Abstract

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with multiple etiological factors. Mannose-binding lectin (MBL) plays a key role in innate immunity by activating antibody-independent lectin complement pathway, opsonisation, phagocytosis, and immune complex (IC) clearance. Genetic polymorphisms in the promoter and coding regions of MBL gene affect the circulatory levels and biological activity of MBL. Defects in MBL can lead to defective opsonisation and, hence, hamper clearance of apoptotic debris, the persistence of which can drive autoantibody formation in lupus. The exon1 variants at codon 52, 54, and 57 have been reported to augment the risk of SLE in different ethnic populations. Three hundred South Indian Tamil patients with SLE and 460 age-, sex-, and ethnicity-matched controls were genotyped for three polymorphisms at codon 52, 54, and 57 in exon1 of MBL gene by Taqman real-time PCR. The three polymorphisms in exon1 of MBL were observed not to confer risk of developing SLE. However, MBL codon 54 rs1800450 polymorphism was associated with the development of medium vessel vasculitis and gangrene (OR-2.29, CI 95% 1.08–4.83, p = 0.02), whereas, the ancestral allele G conferred protection (OR-0.44, CI 95% 0.21–0.93, p = 0.02). Genetic variants in the exon1 of MBL gene per se are not risk factors for SLE in South Indian Tamils. However, the association of codon 54 (rs1800450) with medium vessel vasculitis suggests that it may be a genetic modifier of clinical phenotype in SLE.

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Abbreviations

ACR:

American College of Rheumatology

BD:

Behcet’s disease

IC:

Immune complexes

KD:

Kawasaki disease

MBL:

Mannose-binding lectin

SLE:

Systemic lupus erythematosus

SLEDAI:

Systemic Lupus Erythematosus Disease Activity Index

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Acknowledgments

The study was supported by a financial grant from the Department of Science and Technology, Govt. of India (Grant No. SR/SO/HS-67/2004 dated 03.08.2007).

Authors’ contribution

VN and RG conceived the study. VN, RG, PTA, VKJ, JBU, and DPM recruited the patients for the study. PD carried out genotyping and laboratory workup. PD, DPM, JBU, and VKJ performed statistical analysis. All authors contributed to writing and critically evaluating the manuscript. VSN is the senior investigator and takes primary responsibility for the data.

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Authors and Affiliations

  1. Department of Clinical Immunology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, 605 006, India

    Vir Singh Negi, Panneer Devaraju, Durga Prasanna Misra, Vikramraj K Jain, Jignesh Babulal Usdadiya & Paul T Antony

  2. Genetic Services Unit, Department of Paediatrics, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, 605 006, India

    Reena Gulati

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  1. Vir Singh Negi
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Correspondence to Vir Singh Negi.

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Negi, V.S., Devaraju, P., Misra, D.P. et al. Mannose-binding lectin (MBL) codon 54 (rs1800450) polymorphism predisposes towards medium vessel vasculitis in patients with systemic lupus erythematosus. Clin Rheumatol 36, 837–843 (2017). https://doi.org/10.1007/s10067-017-3539-3

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  • DOI: https://doi.org/10.1007/s10067-017-3539-3

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