MHC class II deficiency D81.6

MHC class II deficiency (major histocompatibility complex/MHC/II deficiency) is a rare (<200 patients worldwide) autosomal recessive primary immunodeficiency caused by LOF mutations in genes of various transcription factors. These mutations lead to a deficiency of MHC class II molecules and ultimately to a disruption of gene regulation. The affected genes encode 4 different regulatory proteins, transcription factors that control the transcription of MHC class II genes. The following genes are affected:

• CIITA
• RFXANK
• RFX51
• RFXAP

Their gene products control the transcription of MHC II molecules.

While the MHC class I complex primarily presents cytosolic peptides, the MHC class II complex primarily presents the cleavage products of exogenous proteins.
Antigen presentation via the MHC II complex occurs mainly on B cells and monocytes. Under the influence of interferon-gamma, this expression is enhanced, or also de-novo expressed on primarily class II negative cells such as fibroblasts or activated T cells.

Mutations in the RFXANK gene are responsible for >70% of all known patients worldwide (Hanna S et al. 2014).

Recurrent sinubronchial abscess and mycotic infections. Recurrent herpes simplex virus infections. Proceeds in principle like other combined immunodeficiencies without phenotypic specifics.

The diagnosis can be made by means of flow cytometry. It can be determined that MHC II is absent on cells on which it is normally expressed (such as B cells and monocytes). Total leucocyte counts are normal. CD4 cells are mostly decreased. Serum immunoglobulins are also decreased. Note: Specific antibodies cannot be produced after vaccination.

The clinical picture of the MHC II defect, corresponds to that of a relatively mild combined immunodeficiency (SCID) with recurrent bacterial and kyotic respiratory and skin infections. Finally, a stem cell transplantation in enstrp. centers is inevitable.

1. Cai YQ et al (2020) A Novel RFXANK Mutation in a Chinese Child With MHC II Deficiency: Case Report and Literature Review. Open Forum Infect Dis 7:ofaa314.
2. Cerundolo V et al (2006) Description of HLA class I- and CD8-deficient patients: Insights into the function of cytotoxic T lymphocytes and NK cells in host defense. Semin Immunol 18: 330-336
3. de la Calle-Martin O et al (2001) Familial CD8 deficiency due to a mutation in the CD8 alpha gene. J Clin Invest 108: 117-123
4. Hanna S et al (2014) MHC class I and II deficiencies. J Allergy Clin Immunol 134:269-275.
5. Hauber I et al (1996) More on MHC class II deficiency. N Engl J Med 335: 977-978.
6. Kallen ME et al (2015) Type II bare lymphocyte syndrome: role of peripheral blood flow cytometry and utility of stem cell transplant in treatment.J Pediatr Hematol Oncol 37:e245-249.
7. Soe KC et al (2013) Transcriptional coactivator CIITA, a functional homolog of TAF1, has kinase activity. Biochim Biophys Acta 1829:1184-1190.