Churg-Strauss syndrome: serum markers of lymphocyte activation and endothelial damage.
OBJECTIVE
To find serologic markers of disease activity in patients with Churg-Strauss syndrome (CSS) linked to possible pathogenetic mechanisms by studying endothelial cell damage (soluble thrombomodulin [sTM]) in relation to T cell and eosinophil activation markers (soluble interleukin-2 receptor [sIL-2R] and eosinophil cationic protein [ECP]), and the presence of autoantibodies (antineutrophil cytoplasmic antibodies [ANCA] and anti-endothelial cell antibodies [AECA]) during both active and inactive phases of disease.


METHODS
Sixteen consecutive patients who fulfilled the 1992 Chapel Hill definition of CSS were studied over a period of 4.5 +/- 3.9 years (mean +/- SD). ECP was detected by Columbo immunocapture (immunoCAP) assay, sIL-2R and sTM by enzyme-linked immunosorbent assay (ELISA), AECA by cell ELISA, and ANCA by indirect immunofluorescence and ELISA.


RESULTS
In patients with active disease, ECP (8.4 +/- 90 units/ml), sIL-2R (3,725 +/- 2,310 units/ml), and sTM levels (5.5 +/- 2.9 units/liter) were significantly elevated compared with those in remission. Levels of sIL-2R showed a close correlation with levels of sTM (r = 0.75, P < 0.05). Interestingly, during remission, sIL-2R levels remained elevated in 4 of 7 patients, although the erythrocyte sedimentation rate, C-reactive protein level, and sTM level returned to the normal range (levels > 1,000 units/ml were associated with relapse). ANCA were found in only 7 patients (4 had classic ANCA, 3 had perinuclear ANCA), and AECA in 11 sera from 8 patients. In contrast to AECA, ANCA were associated with active disease.


CONCLUSIONS
In its active state, CSS is associated with markedly increased levels of sIL-2R and ECP, indicating T cell and eosinophil activation. Elevated sTM is a sign of endothelial cell damage that can be closely linked to T cell activation, as indicated by increased sIL-2R levels.
Schmitt
W H
WH
Medical University of Lübeck, Bad Bramstedt, Germany.
Csernok
E
E
Kobayashi
S
S
Klinkenborg
A
A
Reinhold-Keller
E
E
Gross
W L
WL
D000293:Adolescent; D000328:Adult; D000368:Aged; D000906:Antibodies / Q000032:analysis; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood; D001798:Blood Proteins / Q000032:analysis; D015267:Churg-Strauss Syndrome / Q000097:blood* / Q000473:pathology* / Q000628:therapy; D004730:Endothelium, Vascular / Q000276:immunology / Q000473:pathology*; D047091:Eosinophil Granule Proteins; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D008213:Lymphocyte Activation / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D015375:Receptors, Interleukin-2 / Q000097:blood; D012260:Ribonucleases; D012995:Solubility; D018180:Thrombomodulin / Q000097:blood
D000906:Antibodies; D019268:Antibodies, Antineutrophil Cytoplasmic; D001798:Blood Proteins; D047091:Eosinophil Granule Proteins; D018836:Inflammation Mediators; D015375:Receptors, Interleukin-2; D018180:Thrombomodulin; D012260:Ribonucleases