Patients with inflammatory bowel disease may have a transforming growth factor-beta-, interleukin (IL)-2- or IL-10-deficient state induced by intrinsic neutralizing antibodies.
Ulcerative colitis (UC) and Crohn's disease (CD) are considered to be immunologically mediated disorders that share certain features with murine models of colitis. Whether any of these models are physiologically relevant to the human condition remains controversial. The hypothesis is that increased amounts of antibodies neutralizing transforming growth factor (TGF)-beta, interleukin (IL)-2 or IL-10 create a relative immunodeficient state in inflammatory bowel disease (IBD) that predisposes to disease. To evaluate this, serum samples from patients with UC or CD and from normal healthy individuals were studied by enzyme-linked immunosorbent assays. Antibodies recognizing TGF-beta were most prevalent in UC (P<0.01); anti-IL-10 antibodies were elevated in CD (P<0.05), while anti-IL-2 antibodies were the same for all three groups. Importantly, the percentage of IBD patients with at least one of the antibody levels greater than any control value was 30% for UC and 33% for CD. To verify the presence of these antibodies, immobilized TGF-beta was exposed to UC sera and the attached proteins identified by Western blot assay. The proteins proved to be exclusively immunoglobulin (Ig) G. To evaluate the neutralizing activity of these antibodies, cytokine-specific IgG from subjects in each group of patients was incubated with TGF-beta, IL-2 or IL-10 before addition to a bioassay with changes in viability determined by a colorimetric analysis. Antibodies from most individuals in all three groups neutralized the action of each cytokine. This study shows that about one-third of IBD patients may have a relative deficiency of TGF-beta, IL-2 or IL-10 due to an increase in neutralizing antibodies in their sera.
Ebert
E C
EC
Department of Medicine, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ, USA. ebertec@umdnj.edu
Panja
A
A
Das
K M
KM
Praveen
R
R
Geng
X
X
Rezac
C
C
Bajpai
M
M
D000328:Adult; D000704:Analysis of Variance; D001323:Autoantibodies / Q000032:analysis* / Q000276:immunology / Q000494:pharmacology; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D003093:Colitis, Ulcerative / Q000276:immunology*; D003424:Crohn Disease / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis / Q000276:immunology; D016753:Interleukin-10 / Q000172:deficiency*; D007376:Interleukin-2 / Q000172:deficiency*; D008297:Male; D008875:Middle Aged; D018709:Statistics, Nonparametric; D016212:Transforming Growth Factor beta / Q000172:deficiency*
D001323:Autoantibodies; D007074:Immunoglobulin G; D007376:Interleukin-2; D016212:Transforming Growth Factor beta; D016753:Interleukin-10