Plasma levels of soluble interleukin 2 receptor, soluble CD30, interleukin 10 and B cell activator of the tumour necrosis factor family during follow-up in vasculitis associated with proteinase 3-antineutrophil cytoplasmic antibodies: associations with disease activity and relapse.
OBJECTIVE
To evaluate whether T cell activation, as reflected by levels of soluble interleukin 2 receptor (sIL2R), soluble CD30 (sCD30), IL-10 and B cell activator of the tumour necrosis factor family (BAFF) at diagnosis and during initial follow-up, is predictive for persistent or renewed antineutrophil cytoplasmic antibody (ANCA) positivity and clinical relapse in patients with vasculitis associated with proteinase 3-antineutrophil cytoplasmic antibodies (PR3-ANCA).


METHODS
87 Patients with PR3-ANCA-associated vasculitis and at least 2 years of follow-up were included in the study. At diagnosis, and at 3, 6, 12, 18 and 24 months after diagnosis, cytoplasmic ANCA titres were detected by indirect immunofluorescence (IIF), and PR3-ANCA, sIL2R, sCD30, IL-10 and BAFF levels were assessed by ELISA. 31 healthy volunteers provided plasma samples for comparison. Levels of immune markers were related to ANCA positivity and relapse during follow-up.


RESULTS
Plasma levels of sIL2R, sCD30 and BAFF were higher in patients than in controls at all time points. Plasma levels of sIL2R, sCD30 and IL-10 were higher at diagnosis and relapse than during remission. At 18 months, sCD30 (p<0.001) and sIL2R levels (p = 0.01) were significantly higher in PR3-ANCA-positive patients (detected by ELISA) than in PR3-ANCA-negative patients. ANCA-positive patients detected by ELISA or IIF at 24 months had significantly higher plasma sCD30 levels (p = 0.02 and p = 0.03, respectively) than ANCA-negative patients.


CONCLUSIONS
Increased T cell activation in patients with ANCA-associated vasculitis in remission during and after immunosuppressive treatment is associated with persistent or renewed ANCA positivity.
Sanders
J-S F
JS
Department of Internal Medicine, Division of Clinical Immunology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 GZ Groningen, The Netherlands. j.sanders@int.umcg.nl
Huitma
M G
MG
Kallenberg
C G M
CG
Stegeman
C A
CA
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood; D053264:B-Cell Activating Factor; D015415:Biomarkers / Q000097:blood; D003520:Cyclophosphamide / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016753:Interleukin-10 / Q000097:blood; D017730:Ki-1 Antigen / Q000097:blood; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008565:Membrane Proteins / Q000097:blood; D008875:Middle Aged; D053146:Myeloblastin; D011239:Prednisolone / Q000627:therapeutic use; D015375:Receptors, Interleukin-2 / Q000097:blood; D012189:Retrospective Studies; D012697:Serine Endopeptidases / Q000276:immunology; D012720:Severity of Illness Index; D012995:Solubility; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha; D014657:Vasculitis / Q000188:drug therapy / Q000276:immunology*
D019268:Antibodies, Antineutrophil Cytoplasmic; D053264:B-Cell Activating Factor; D015415:Biomarkers; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D017730:Ki-1 Antigen; D008565:Membrane Proteins; D015375:Receptors, Interleukin-2; C505719:TNFSF13B protein, human; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D003520:Cyclophosphamide; D011239:Prednisolone; D012697:Serine Endopeptidases; D053146:Myeloblastin