Catalase and α-enolase: two novel granulocyte autoantigens in inflammatory bowel disease (IBD)

Abstract

SUMMARYIn IBD, the target antigens of anti-neutrophil cytoplasmic autoantibodies (ANCA) have not been fully identified, which limits the analysis of the diagnostic significance as well as of the possible pathophysiological role of these antibodies. In this study, we identify the target antigens of ANCA in large groups of patients with ulcerative colitis (UC) and Crohn's disease (CD). Apart from antibodies against lactoferrin and bactericidal/permeability-increasing protein (BPI), which have been reported before, antibodies against two novel granulocyte antigens were identified: antibodies against a 57/56-kD doublet were found in 38% of samples from UC patients and in 26% of samples from CD patients, whereas antibodies against a 47-kD protein were found in 10% of samples from UC patients and in 18% of samples from CD patients. Partial purification and amino acid sequence analysis identified the 57-kD protein as catalase and the 47-kD protein as a-enolase. This study is the first to report catalase and a-enolase as granulocyte antigens for autoantibodies in IBD.

Anti-Alpha-Enolase Antibody as a Serologic Marker and Its Correlation with Disease Severity in Intestinal Behçet’s Disease

“…In our study, IgM AAEA was positive in 54 of 80 (67.5%) intestinal BD patients, which was higher than the prevalence among BD patients (45.0%) reported by Lee et al [13]. The rate of AAEA positivity was higher in intestinal BD than in other inflammatory bowel diseases, such as UC (10%) and CD (21%) [25]. Therefore, IgM AAEA may be a useful serologic marker of intestinal BD, similar to the use of ASCA in CD and pANCA in UC, especially in patients with intestinal involvement who lack systemic manifestations of BD.…”

Identification of Rat Targets of Anti-Soluble Liver Antigen Autoantibodies by Serologic Proteome Analysis

“…4,2003 plasm in patients with autoimmune liver disease or inflammatory bowel disease, in whom ␣-enolase antibodies are frequently detected (38,39 ). Interestingly, antienolase and anti-catalase antibodies, as anti-SLA antibodies, have been described as being undetectable by IIF (23,39 ). Affinity measurements coupled with isoform and epitope mapping of both anti-catalase and anti-␣-enolase in different pathologies seem to be necessary to obtain a clear understanding of their broad distribution.…”

Serologic Markers in Inflammatory Bowel Disease

“…This is particularly the case for the cytoplasmic autoantigens, which are not packed and concentrated in granules. For example, only 21% and 38% of IBD samples positive for antibodies to catalase and ␣-enolase, respectively, were positive for ANCA antibodies by indirect immunofluorescence (27 ).…”

“…Overviews of the various studies (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28) ) that have attempted to identify the antigenic species recognized by atypical P-ANCAs in UC and CD patients and in controls are given in Tables 1 through 3. The antigens that have been studied are located in the granules, the cytosol, and/or the nuclei or nuclear periphery.…”

“…This means that in the majority of the studies, the cutoff was chosen in a way such that positive results were found in only a small portion of the healthy control population. In one study, in which Western blotting was used to detect antibodies, anti-BPI, anti-elastase, anti-catalase, and anti-␣-enolase antibodies were found in 0%, 0%, 10%, and 5% of healthy controls, respectively (27 ). A shortcoming of many studies is that the antibodies have been studied in welldefined CD or UC patients but not in diseased controls, i.e., non-IBD patients (e.g., infective diarrhea) who present with symptoms similar to the symptoms in IBD.…”