Differential B- and T-cell activation in Wegener’s granulomatosis,☆☆,

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Abstract

Background: Autoimmune mechanisms are postulated to play a role in the development and progression of Wegener’s granulomatosis (WG), a form of systemic, idiopathic necrotizing vasculitis. Objective: We investigated the relation between lymphocyte activation and disease activity in patients with WG. Methods: B- and T-lymphocyte activation was studied by cytometric assessment of the expression of the activation markers CD38 on B cells and CD25 and HLA-DR on CD4+ and CD8+ T-cell subsets, respectively. Activation at the cellular level was related to serum levels of antineutrophil cytoplasmic antibodies and soluble IL-2 receptor, which can be regarded as soluble activation markers of B and T cells. Results: Percentages of CD38bright activated B cells were higher in patients with active WG than in patients experiencing disease remission (P < .05) or in healthy control subjects (P < .05). Percentages of activated CD4+ and CD8+ T cells were higher in patients with active WG (CD4 subset, P < .0001; CD8 subset, P < .005) than in healthy individuals. An increased percentage of activated T cells of both subsets was also seen in patients whose condition was in remission, as compared with healthy control subjects (CD4 subset, P < .0005; CD8 subset, P < .001). Lymphocyte activation at the cellular level did not correlate with plasma levels of antineutrophil cytoplasmic antibodies or soluble IL-2 receptor. Conclusion: In WG, B-cell activation is related to active disease, whereas T-cell activation persists during remission of the disease, which points to an intrinsic disordered immune system in this disease. (J Allergy Clin Immunol 1999;103:885-94.)

Section snippets

Patients and clinical parameters

Thirty-three consecutive patients (22 men and 11 women; mean age, 55 years; range, 19 to 86 years) who fulfilled the classification criteria of the American College of Rheumatology for the diagnosis of WG18 were included in this cross-sectional study. All patients had ANCA with specificity for proteinase 3 at diagnosis. Eight of the 33 patients were studied at first examination of the disease. All other patients were diagnosed 33 months or longer (mean, 103 months; range, 33 to 256 months)

Clinical parameters

Serum titers of ANCA, as determined by IIF, are shown in Table I. Anti-PR3 ANCA levels, as measured by direct ELISA, were significantly higher in patients with active WG than in patients with quiescent disease (P < .005; Fig 1).

. Plasma levels of anti-PR3 ANCA in relation to disease activity and extent. P values for each patient group were determined relative to healthy control subjects (*) or relative to another patient group (* above line ). Indicated are the 10th, 25th, 50th, 75th, and 90th

DISCUSSION

In this study we investigated the relation between cellular and humoral immunity in WG in relation to disease activity and the interrelationship of B- and T-cell activation. We found a differential activation pattern of lymphocytes where B-cell activation correlated with active disease, whereas increased T-cell activation persisted during complete remission.

CD38 was used as a marker of B-cell activation and differentiation.27 CD19+/CD38bright, blast-like B cells were present at a higher

Acknowledgements

The authors thank G. Mesander for valuable help with flow cytometry and Dr P. C. Limburg for helpful suggestions and criticism concerning this work.

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    Supported by the European Community “Human Capital and Mobility,” grant ERBCHBGCT940627, and by the Dutch Kidney Foundation, grant C97.1663.

    ☆☆

    Reprint requests: Eliane R. Popa, MSc, Department of Clinical Immunology, University Hospital, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.

    0091-6749/99 $8.00 + 0  1/1/97165

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