Correspondence

More on MHC Class II Deficiency

N Engl J Med 1996; 335:977-978September 26, 1996

Article

To the Editor:

The expression of major-histocompatibility-complex (MHC) class II genes (HLA-DR, DP, and DQ) is tightly regulated at the transcriptional level.1 The complete absence of MHC class II molecules on all the cells of patients with MHC class II deficiency has been attributed to regulatory defects in the transcription of these genes.1 Recently, we identified twins with a noteworthy phenotype of MHC class II deficiency.2 The defect in these patients did not appear to affect all types of cells and all the genes at the HLA-D locus to the same extent.3 In cells from healthy people, the expression of MHC class II genes can be induced by external stimuli — for example, by interferon gamma.1 We and others have previously failed to demonstrate the induction of such gene expression by interferon gamma in patients with MHC class II deficiency.2,4

We report an analysis of MHC class II gene expression induced by interferon gamma in a four-year-old girl with MHC class II deficiency and autoimmune hemolytic anemia who had autoantibodies against the Rh e antigen.5 The reverse-transcriptase polymerase chain reaction (RT-PCR) showed that expression of the HLA-DP (Figure 1Figure 1Southern Blot Analysis of Amplified Complementary DNA from Unstimulated Peripheral-Blood Mononuclear Cells and Those Treated with Interferon Gamma.), DR, and DQ (data not shown) genes was defective in the patient's unstimulated plastic-adherent fraction of peripheral-blood mononuclear cells (containing mainly cells of the monocyte–macrophage lineage) and the nonadherent fraction (containing mainly T cells, B cells, and natural killer cells). Interestingly, stimulating the patient's mononuclear cells for 24 hours with recombinant human interferon gamma (500 IU per milliliter) induced a substantial increase in levels of HLA-DPβ₁ messenger RNA in each of the two fractions. However, expression of the genes coding for HLA-DPα was still defective after the treatment with interferon gamma (Figure 1), as was expression of the genes for HLA-DR and DQ (data not shown).

These findings indicate that in addition to the genetic defects described, previously unrecognized defects in the complex regulation of class II gene expression may be present in patients with MHC class II deficiency. The pattern of MHC class II gene expression that can be induced by treatment with interferon gamma in a patient with MHC class II deficiency is noteworthy. Besides the coordinated up-regulation of MHC class II expression previously described,1 cell type, chain-specific factors, or both may be involved in the interferon gamma–regulated induction of MHC class II gene expression in this patient. There may be a relation between the abnormal regulation of such gene expression and the production of autoantibodies, as we observed in this case.

Ilona Hauber, Ph.D.
Hermann M. Wolf, M.D.
Martha M. Eibl, M.D.
University of Vienna, A-1090 Vienna, Austria

Volker Wahn, M.D.
University Children's Hospital, D-40225 Düsseldorf, Germany

5 References

1. 1

   Reith W, Steimle V, Mach B. Molecular defects in the bare lymphocyte syndrome and regulation of MHC class II genes. Immunol Today 1995;16:539-546
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2. 2

   Wolf HM, Hauber I, Gulle H, et al. Twin boys with major histocompatibility complex class II deficiency but inducible immune responses. N Engl J Med 1995;332:86-90
   Full Text | Web of Science | Medline

3. 3

   Hauber I, Gulle H, Wolf HM, Maris M, Eggenbauer H, Eibl MM. Molecular characterization of major histocompatibility complex class II gene expression and demonstration of antigen-specific T cell response indicate a new phenotype in class II-deficient patients. J Exp Med 1995;181:1411-1423
   CrossRef | Web of Science | Medline

4. 4

   de Preval C, Hadam MR, Mach B. Regulation of genes for HLA class II antigens in cell lines from patients with severe combined immunodeficiency. N Engl J Med 1988;318:1295-1300
   Full Text | Web of Science | Medline

5. 5

   Horneff G, Seitz RC, Stephan V, Wahn V. Autoimmune haemolytic anaemia in a child with MHC class II deficiency. Arch Dis Child 1994;71:339-342
   CrossRef | Web of Science | Medline