Rationale Major histocompatibility complex class II (MHC II) deficiency is a rare immune disorder characterized by defective transcription of MHC II genes and absent protein expression. This disorder has primarily been described in consanguineous families of European and North African descent. We present a sporadic case in an American female infant.
Methods G.C. presented at age 3½ months with Pneumocystis pneumonia, respiratory failure, and protracted diarrhea. Initial immune studies showed primarily CD4 but intermittently CD8 lymphopenia, hypogammaglobulinemia, and near-normal mitogen responses. Bone marrow transplant (BMT) evaluation, including high-resolution human leukocyte antigen (HLA) genotyping, was performed. BMT was deferred due to the family's wishes after clinical improvement. Despite immunoglobulin replacement therapy and antimicrobial prophylaxis, she subsequently developed pseudomonal otitis, Pneumocystis pneumonia, Salmonella/Giardia enteritis, and enteroviral meningoencephalitis. At age 2½ years, she had persistent CD4 lymphopenia, hypogammaglobulinemia, and declining mitogen responses. Surface expression of MHC II was absent by serology and flow cytometry. She is currently awaiting BMT.
Results As expected, expression of MHC II genes was normal by PCR. Flow cytometry demonstrated deficient HLA-DR expression on lymphocytes (0.16% vs control 5.3%; mean fluorescence intensity [MFI] 30.5 vs 206) and monocytes (2.7% vs control 94%, MFI 31 vs 171). RT-PCR analysis of MHC II promoter-binding transcription factors is in process.
Conclusions MHC II deficiency should be a diagnostic consideration in children with combined immune deficiency and early, definitive treatment with BMT performed prior to onset of infections. Normal expression of MHC II genes by PCR does not exclude this diagnosis and MHC II protein expression must be measured.
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