Lupus (SLE)

HLA-DRB1*03:01 · C4-Null

Systemic lupus erythematosus is an autoimmune disease that can affect many organs. In the HLA region two layers act together: class II types such as DRB1*03:01 and DRB1*15:01 raise risk, and defects of the complement component C4 in the class III region weaken the clearance of cell debris.

Two layers in the MHC region

The class II types influence the presentation of autoreactive peptides. In the class III region lie the C4 genes of the complement system, whose copy number varies; if C4 is missing, accumulating cell debris is cleared less well and can trigger autoantibodies. Thus different parts of the same region contribute in different ways.

Context

The individual HLA contributions are moderate and only part of a strongly polygenic risk. The diagnosis rests on clinical findings and autoantibodies. Genome shows the HLA types and the class III context as technical evidence.

What Genome measures. Presence of risk class II types (DRB1*03:01, DRB1*15:01) and indications of C4 null alleles or low C4 copy number in the MHC class III region.

Related topics

HLA and autoimmunityAutoimmune thyroid (Hashimoto, Graves)HLA typing

Sources

  1. 1Deng & Tsao, 2010 Genetic susceptibility to systemic lupus erythematosus in the genomic era. Nature Reviews Rheumatology 6:683–692. doi.org/10.1038/nrrheum.2010.176
  2. 2Goulielmos et al., 2018 The genetics and molecular pathogenesis of systemic lupus erythematosus in populations of different ancestry. Gene 668:59–72. doi.org/10.1016/j.gene.2018.04.038