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HLA and KIR Gene Polymorphism in Lupus Nephritis Patients from Western India

Background: Systemic Lupus Erythematosus (SLE) is a complex multifactorial chronic autoimmune disorder characterized by humoral autoimmunity. The etiology of SLE is thought to involve an interplay of environmental, humoral, and genetic factors. Lupus nephritis (LN) is the most common clinical manifestation seen in SLE patients causing increased morbidity and mortality. There is a strong association of the human leukocyte antigen (HLA) and Killer Cell Immunoglobulin- Like Receptor (KIR) with SLE, however, the association is likely to be heterogeneous among different ethnic groups. The aim of this study was to determine the association of HLA and KIR genes in susceptibility and clinical manifestations of LN in SLE patients of western Indian population.

Methods: A total of 97 SLE patients with LN and 150 SLE patients without LN fulfilling the ACR criteria for SLE and the World Health Organisation (WHO) classification for lupus nephritis were recruited. A total of 250 age sex and ethnically matched normal healthy controls were recruited for this study.

HLA types were determined by the polymerase chain reaction on a Luminex platform with sequence-specific oligonucleotide primers (SSOP) method. Presence or absence of KIR gene polymorphism was studied using the duplex PCR sequence specific primer (SSP) technique

Results: The following HLA alleles were found to be positively associated with LN: HLA-DRB1*01 (P=0.0237), HLA DRB1*10 (P=0.0107), HLA DQB1*05(P=0.0167) and DQA1*01(P=0.0049). The HLA alleles found to be protective of LN were HLA DRB1*11 (P=0.0121) and HLA-DQB1*03 (P=.0005). Higher frequency iKIR 2DL2 was associated with LN whereas lower frequency of iKIR 2DL1, 2DL3 and aKIR2DS4 were associated with LN.

Conclusions: Our data suggest an association between HLA class II and iKIR 2DL2 with susceptibility to LN in SLE in the Indian population. HLA-DRB1*01, HLA DRB1*10, HLA DQB1*05 and DQA1*01 are strongly positively associated with SLE in western Indian SLE patients. DRB1*11 and DQB1*03 are negatively associated with SLE in western India.

Author(s): Leenam Dedhia, Vandana Pradhan, Kanjaksha Ghosh, Milind Nadkar and Sunil Parekh

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