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Common variable immunodeficiency (CVID) and MxA-protein expression in blood leucocytes
J A Rump1, D Jakschiess, U Walker
1Abteilung Rheumatologie, Med. Univ. Klinik, Freiburg, Germany.
Insights
This study investigated Common Variable Immunodeficiency (CVID) pathogenesis. MxA-protein levels in patients suggest neither chronic viral infections nor autoimmune diseases are the primary cause of CVID.
Area of Science:
- Immunology
- Virology
- Autoimmunity
Background:
- Common Variable Immunodeficiency (CVID) pathogenesis is unclear, with suspected links to chronic viral infections or autoimmune conditions.
- MxA-protein in leukocytes indicates interferon system activation, a marker for viral and autoimmune diseases.
- Formal proof for viral involvement in CVID is currently lacking.
Purpose of the Study:
- To investigate the immunopathogenic mechanism of CVID by assessing MxA-protein expression.
- To determine if chronic viral infection or autoimmune conditions contribute to CVID.
- To evaluate the host's interferon system activation in CVID patients.
Main Methods:
- Measured MxA-protein levels in leukocyte lysates from 15 patients with hypogammaglobulinaemia (13 CVID, 1 hyper-IgM, 1 B-CLL with HPV).
- Assessed MxA-protein expression in vivo and in vitro response to interferon-alpha (IFN-alpha).
- Correlated MxA expression with CD4/CD8 ratios and CD8/CD57+ T cell counts.
Main Results:
- Only one patient (B-CLL with HPV) showed strong MxA-protein expression; two CVID patients were borderline, and 12 were negative.
- No correlation was found between MxA expression and low CD4/CD8 ratios or increased CD8/CD57+ T cells.
- Peripheral blood leukocytes from MxA-negative CVID patients produced normal MxA-protein levels upon in vitro IFN-alpha stimulation.
Conclusions:
- The findings argue against a chronic viral or autoimmune pathogenesis for Common Variable Immunodeficiency (CVID).
- MxA-protein expression is not a reliable indicator of underlying viral or autoimmune processes in most CVID patients.
- Further research is needed to elucidate the specific immunopathogenic mechanisms of CVID.
Abstract:
The underlying immunopathogenic mechanism of CVID has been suspected to involve a chronic viral infection or an autoimmune condition. However, formal proof of viral infection is lacking. Measurement of MxA-protein in leucocyte lysates is a sensitive test for evaluating the activation of the host's interferon system. Both viral infections and autoimmune diseases such as systemic lupus erythematosus (SLE) strongly induce MxA-protein in peripheral leucocytes. We therefore examined 15 patients with longlasting hypogammaglobulinaemia for MxA-protein induction in vivo: 13 patients suffered from CVID, one from hyper-IgM syndrome, and one patient had chronic B lymphocytic leukaemia associated with immunoglobulin deficiency and chronic papilloma virus infection (condylomata accuminata). Only the latter patient exhibited a strong MxA-protein expression; two CVID patients were borderline positive, and the remaining 12 patients including the hyper-IgM syndrome were MxA-protein-negative. There was no relationship between MxA expression and low CD4/CD8 ratios or increased CD8/CD57+ T cell counts, although both conditions are often observed in CVID as well as in chronic viral infections. When exposed in vitro to interferon-alpha (IFN-alpha), peripheral blood leucocytes of four MxA-negative patients were capable of producing normal amounts of MxA-protein. Taken together, these results argue against a viral or autoimmune pathogenesis of CVID.