Immune Status and Risk for Infection in Patients Receiving Chronic Immunosuppressive Therapy

THOMAS GLÜCK, BERNHARD KIEFMANN, MATHIAS GROHMANN, WERNER FALK, RAINER H. STRAUB, and JÜRGEN SCHÖLMERICH

ABSTRACT.

Objective. Chronic immunosuppressive therapy may be complicated by infections indicating a more or less profound immune defect. However, immune monitoring to estimate the risk for infection has so far not been performed routinely. The aim of this study was (1) to investigate the effects of commonly used immunosuppressive treatment regimens on lymphocyte subsets and cytokine release from stimulated whole blood cultures in patients with rheumatic or autoimmune diseases; and (2) to determine whether such measurements could be used as predictors of infection, and if so, to determine their predictive value for subsequent infectious complications.

Methods. Patients with various chronic inflammatory diseases (n = 97) treated with different immunosuppressive regimens and healthy controls (n = 36) were evaluated for T lymphocyte subsets and for cytokine release in whole blood cultures after stimulation with lipopolysaccharide (LPS) or phorbol myristate acetate (PMA) and ionomycin.

Results. Therapy with corticosteroids induced dose-dependent lymphocyte depletion. Concomitant application of cytotoxic disease modifying drugs and corticosteroids caused an additive effect on lymphocytopenia, but did not change CD4/CD8 ratio. Corticosteroid therapy was also associated with impaired cytokine release from mononuclear cells in whole blood assays after in vitro stimulation with LPS or PMA/ionomycin. Infections requiring hospitalization developed in 19 of 95 evaluable patients during an average followup period of 2.3 years. On logistic regression analysis, lymphocytopenia < 600/µl, in particular < 250 CD4+ T cells/µl, and therapy with corticosteroids > 10 mg prednisolone equivalent per day were predictive of infections. Multiple logistic regression analysis showed that T-helper lymphocytopenia < 250/µl was the best predictor for future infections, with a positive predictive value of 0.53 and a negative predictive value of 0.97.

Conclusion. Patients receiving chronic immunosuppressive therapy can develop severe lymphopenia that involves all subsets. Monitoring T-helper cell counts may be useful to estimate the risk for subsequent infections in such patients. (J Rheumatol 2005;32:1473-80)

Key Indexing Terms:

CHRONIC IMMUNOSUPPRESSIVE THERAPY
RHEUMATIC DISEASES
LYMPHOCYTE SUBSETS
CYTOKINES
WHOLE BLOOD ASSAYS

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From the Division of Infectious Diseases, Division of Rheumatology, Department of Internal Medicine I, University Medical Center, University of Regensburg, Regensburg, Germany.

Supported by University Medical Center, University of Regensburg.

T. Glück, MD, Senior Lecturer in Medicine; B. Kiefmann, MD; M. Grohmann, MD; W. Falk, PhD, Associate Professor of Medicine; R.H. Straub, MD, Associate Professor of Medicine; J. Schölmerich, MD, Professor of Medicine.

Address reprint requests to Dr. T. Glück, Division of Infectious Diseases, Division of Rheumatology, Department of Internal Medicine I, University Medical Center, University of Regensburg, D-93042 Regensburg, Germany. E-mail: thomas.glueck@klinik.uni-regensburg.de

Accepted for publication March 29, 2005.

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