Beta-2 Microglobulin – Major Histocompatibility Complex Class I Deficiency

Autosomal recessive β2-microglobulin (B2M) deficiency due to bi-allelic splice-site variant c.67+1G>T results in Major Histocompatibility Complex class I (MHC-I) deficiency. Two Turkish siblings homozygous for c.67+1G>T presented with recurrent upper and lower respiratory tract infections and severe skin disease or bronchiectasis, and the variant segregated in heterozygous, asymptomatic parents (PMID:25702838).

Immunologic assays including flow cytometry, ELISA, and immunohistochemistry demonstrated absence of polymorphic MHC-I, CD1a, CD1b, CD1c, and neonatal Fc receptor on patient cells, leading to low serum IgG and albumin levels, expansion of CD8+ γδ T cells, and unlicensed natural killer cells. This concordant loss-of-function phenotype supports a haploinsufficiency mechanism without reported conflicting evidence.

Key take-home: β2-microglobulin deficiency should be considered in autosomal recessive immunodeficiency with absent MHC-I expression; molecular diagnosis informs genetic counseling and management.

References

• The Journal of Allergy and Clinical Immunology • 2015 • β2-Microglobulin deficiency causes a complex immunodeficiency of the innate and adaptive immune system PMID:25702838

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