MICA gene

MICA (MHC Class I Polypeptide-Related Sequence A) is a protein-coding gene located on chromosome 6p21.33. Alternative splicing of this gene results in multiple transcript variants.

The MICA- gene encodes the highly polymorphic MIC protein A related to the major histocompatibility complex class I chain. The protein product is expressed on the cell surface, although unlike the canonical class I molecules, it does not appear to associate with beta-2-microglobulin.

In contrast to the ubiquitous expression of classical HLA class I molecules, MIC proteins have a limited tissue distribution, being constitutively expressed on epithelial cells, particularly in the gastrointestinal tract, endothelial cells, fibroblasts, monocytes, keratinocytes, and dendritic cells. MIC molecules are not expressed on resting T or B lymphocytes and, unlike HLA class I antigens, are not upregulated by INF-γ. In addition to the membrane-bound form, a soluble isoform of MICA (sMICA) is also under intense discussion, which has the potential to bind the natural killer cell-activating receptor NKG2D, leading to endocytosis and degradation of the receptor-ligand interaction complex, thereby suppressing NKG2D-mediated host innate immunity.

Variations in the MICA gene have been linked to susceptibility to psoriasis and psoriatic arthritis.

The release of MICA-related antibodies and ligands is involved in the development of monoclonal gammopathy of undetermined significance to multiple myeloma.

MICA genotyping data in 81 Japanese patients with Takayasu arteritis, 38 Japanese patients with thrombangiitis obliterans, and 160 healthy Japanese controls showed that polymorphisms in the MICA gene were significantly associated with Takayasu arteritis and Buerger disease, respectively. MICA-1.2 was shown to have a significantly high OR risk for Takayasu arteritis in the absence of HLA-B52, suggesting that the HLA-linked gene susceptible to Takayasu arteritis mapped near the MICA gene. In contrast, MICA-1.4 resulted in a significantly high OR risk for thrombangiitis obliterans only in the presence of HLA-B54, suggesting that the HLA-linked gene susceptible to Buerger disease is associated with the HLA-B54-MICA-1.4 haplotype and may map differently than the gene for Takayasu arteritis.

1. Kimura A et al (1998) MICA gene polymorphism in Takayasu's arteritis and Buerger's disease. Int J Cardiol 66 Suppl 1:S107-113