Anti-high mobility group box 1 and box 2 non-histone chromosomal proteins (HMGB1/HMGB2) antibodies and anti-Saccharomyces cerevisiae antibodies (ASCA): accuracy in differentially diagnosing UC and CD and correlation with inflammatory bowel disease phenotype.
BACKGROUND
The development of a supportive diagnostic method has long been required to differentially diagnose ulcerative colitis (UC) and Crohn's disease (CD). Several antibodies circulate in the sera of patients with inflammatory bowel disease. We previously identified the high mobility group box 1 and box 2 non-histone chromosomal proteins (HMGB1 and HMGB2) as novel antigens of perinuclear type anti-neutrophil cytoplasmic antibodies (pANCA) and discovered anti-HMGB1/HMGB2 antibodies in sera from patients with UC. Here, we evaluated the ability of anti-HMGB1/HMGB2 antibodies combined with anti-Saccharomyces cerevisiae antibodies (ASCA) to differentially diagnose UC and CD.


METHODS
We measured titers of anti-HMGB1/HMGB2 antibodies and ASCA in the sera of 213 patients with UC and 93 with CD, using enzyme-linked immunosorbent assays.


RESULTS
Among the patients with UC, 26.8% were positive for anti-HMGB1/HMGB2 antibodies, with 85.0% specificity towards CD and a positive predictive value of 80.3%. Corticosteroids significantly suppressed the titer of anti-HMGB1/HMGB2 antibodies. Among the patients with CD, 24.7% were positive for ASCA, with 96.2% specificity towards UC and a positive predictive value of 74.2%. Interestingly, the positivity rate of anti-HMGB/HMGB2 antibodies was higher (35.7%) in patients with the ileitis type of CD than in patients with CD in the colon (6.2%; significant difference, P < 0.01). The specificity of anti-HMGB1/HMGB2 antibodies in UC for CD in the colon was 93.8%.


CONCLUSIONS
CD in the colon and UC can be differentially diagnosed using anti-HMGB/HMGB2 antibodies combined with ASCA.
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Hiromasa
H
Takaishi
Takanori
T
Kanai
Atsushi
A
Nakazawa
Fumihiko
F
Sugata
Akira
A
Nikai
Shigeo
S
Yoshizawa
Yasuo
Y
Hamamoto
Shinsuke
S
Funakoshi
Tomoharu
T
Yajima
Yasushi
Y
Iwao
Masao
M
Takemura
Shoichi
S
Ozaki
Toshifumi
T
Hibi
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000908:Antibodies, Fungal / Q000097:blood; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000276:immunology*; D002868:Chromosomal Proteins, Non-Histone / Q000276:immunology; D003093:Colitis, Ulcerative / Q000175:diagnosis* / Q000276:immunology; D003424:Crohn Disease / Q000175:diagnosis* / Q000276:immunology; D003937:Diagnosis, Differential; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D024243:HMGB1 Protein / Q000276:immunology*; D024261:HMGB2 Protein / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012441:Saccharomyces cerevisiae / Q000276:immunology*; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D055815:Young Adult
D000908:Antibodies, Fungal; D001323:Autoantibodies; D001324:Autoantigens; D002868:Chromosomal Proteins, Non-Histone; D024243:HMGB1 Protein; D024261:HMGB2 Protein