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S R Targan

Publications and source records attributed to S R Targan.

At least 73 records · Page 4Linked to original sources
PubMed1997

A role for TNF-alpha and mucosal T helper-1 cytokines in the pathogenesis of Crohn's disease.

Recent clinical studies of Crohn's disease patients demonstrated dramatic clinical responses following one i.v. infusion of a chimeric mAb to TNF-alpha (cA2). To assess the role of TNF-alpha in mucosal cytokine regulation, the effects of TNF-alpha on lamina propria mononuclear cell (LPMC) Th1 production were determined. Increased IFN-gamma production was demonstrated in anti-CD2-stimulated LPMC cultured in TNF-alpha. To determine the effects of cA2 on cytokine production, TNF-alpha- and IFN-gamma-producing cells were quantitated in LPMC from five Crohn's disease patients treated with cA2. In all four patients who demonstrated clinical and endoscopic improvement, decreased numbers of LPMC producing IFN-gamma and TNF-alpha following CD2/CD28 activation paralleled improvement in disease activity over 8 wk. In one patient who did not improve, increased numbers of TNF-alpha- and IFN-gamma-secreting LPMC were observed. In three of four responding patients, CD2/CD28-activated PBMC demonstrated increased IFN-gamma production over 8 wk. These observations suggest that TNF-alpha may be a cofactor for mucosal Th1 responses, and improvement in clinical parameters and intestinal inflammation induced by cA2 in Crohn's disease may be mediated by down-regulation of mucosal Th1 cytokines.

Adjuvants, Immunologic↗
PubMed1997

A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn's disease. Crohn's Disease cA2 Study Group.

BACKGROUND: Studies in animals and an open-label trial have suggested a role for antibodies to tumor necrosis factor alpha, specifically chimeric monoclonal antibody cA2, in the treatment of Crohn's disease. METHODS: We conducted a 12-week multicenter, double-blind, placebo-controlled trial of cA2 in 108 patients with moderate-to-severe Crohn's disease that was resistant to treatment. All had scores on the Crohn's Disease Activity Index between 220 and 400 (scores can range from 0 to about 600, with higher scores indicating more severe illness). Patients were randomly assigned to receive a single two-hour intravenous infusion of either placebo or cA2 in a dose of 5 mg per kilogram of body weight, 10 mg per kilogram, or 20 mg per kilogram. Clinical response, the primary end point, was defined as a reduction of 70 or more points in the score on the Crohn's Disease Activity Index at four weeks that was not accompanied by a change in any concomitant medications. RESULTS: At four weeks, 81 percent of the patients given 5 mg of cA2 per kilogram (22 of 27 patients), 50 percent of those given 10 mg of cA2 per kilogram (14 of 28), and 64 percent of those given 20 mg of cA2 per kilogram (18 of 28) had had a clinical response, as compared with 17 percent of patients in the placebo group (4 of 24) (p<0.001 for the comparison of the cA2 group as a whole with placebo). Thirty-three percent of the patients given cA2 went into remission (defined as a score below 150 on the Crohn's Disease Activity Index), as compared with 4 percent of the patients given placebo (P=0.005). At 12 weeks, 41 percent of the cA2-treated patients (34 of 83) had had a clinical response, as compared with 12 percent of the patients in the placebo group (3 of 25) (P=0.008). The rates of adverse effects were similar in the groups. CONCLUSIONS: A single infusion of cA2 was an effective short-term treatment in many patients with moderate-to-severe, treatment-resistant Crohn's disease.

Adult↗
PubMed1997

Analysis of intestinal lymphocytes in mouse colitis mediated by transfer of CD4+, CD45RBhigh T cells to SCID recipients.

Transfer of specific T lymphocyte subsets isolated from the spleens of healthy donor mice into immunodeficient SCID mice leads to chronic intestinal inflammation with characteristics similar to those of human inflammatory bowel disease (IBD). CD4+, CD45RBhigh cells cause disease, whereas CD4+, CD45RBlow and CD8+, CD45RBhigh cells do not. Despite this difference, we demonstrate that all three T cell populations reconstitute the intraepithelial and lamina propria compartments of both small and large intestines of SCID recipients. Therefore, infiltration of lymphocytes alone is not sufficient for disease development. CD4+ lymphocytes that have trafficked to the SCID intestine exhibit a phenotype characteristic of normal mucosal lymphocytes. This includes high expression of alpha E integrin and CD69, expression of CD8 alpha alpha homodimers in some of the intraepithelial lymphocytes, as well as low expression of CD62L and CD45RB. The phenotype of the infiltrating mucosal cells is indistinguishable, with respect to the cell surface markers tested, regardless of whether the starting donor population is CD45RBhigh or CD45RBlow. Severe inflammation is restricted primarily to the colon despite lymphocyte infiltration throughout the length of the intestine. This suggests that some property of the colon microenvironment contributes to inflammation. Consistent with this, transfer of CD4+, CD45RBhigh cells to SCID mice that have significantly reduced numbers of enteric flora results in attenuation of the wasting and colitis. Fewer numbers of donor lymphocytes are recovered from the intraepithelial and lamina propria compartments of reduced flora SCID mice. We hypothesize that the ability of pathogenic cells to traffic to the intestine and mediate colitis may be driven by T cell reactivity to bacteria or bacterial products.

Adoptive Transfer↗
PubMed1997

A new syndrome of Crohn's disease and pachydermoperiostosis in a family.

Few syndromic associations with Crohn's disease are described. The aim of this study was to characterize a new syndrome of Crohn's disease associated with pachydermoperiostosis in 3 brothers. Three probands, 6 siblings, both parents, 20 of 21 third-generation relatives, and 9 spousal controls were evaluated. Serological evaluation for antineutrophil cytoplasmic antibodies and human leukocyte antigens as well as genetic testing for tumor necrosis factor microsatellites, intercellular adhesion molecule 1 polymorphisms, the interleukin 1 receptor antagonist gene, and the interleukin 1 beta gene were performed. Only the 3 probands were affected and developed pachydermoperiostosis between ages 14 and 17 years. Pachydermoperiostosis preceded Crohn's ileocolitis by 6 and 20 years in two probands, excluding secondary hypertrophic osteoarthropathy. Two probands were antineutrophil cytoplasmic antibody positive vs. 1 of 27 unaffected relatives (P < 0.001, chi 2). Haplotypes for human leukocyte antigen and tumor necrosis factor microsatellites were discordant. The probands' generation was homozygous for the common allele 1 of the interleukin 1 receptor antagonist and interleukin 1 beta genes. Two probands carried a rare polymorphism of the intercellular adhesion molecule 1 gene. A new syndrome of Crohn's disease and pachydermoperiostosis associated with antineutrophil cytoplasmic antibodies is described. Inheritance is most likely autosomal recessive by pedigree. No clear association was found between this syndrome and the gene regions evaluated.

Adolescent↗
PubMed1996

Phage display cloning and characterization of an immunogenetic marker (perinuclear anti-neutrophil cytoplasmic antibody) in ulcerative colitis.

Ulcerative colitis (UC) is genetically associated with a marker serum Ab (pANCA), identified by its reactivity with a neutrophil Ag. This study utilized phage display technology to clone and characterize pANCA, which has resisted conventional isolation strategies. Since spontaneous pANCA-secreting B cells are detectable in UC lamina propria lymphocytes, this cell source was used to construct a complete IgG1-kappa Ig library. Selection of phage by panning with fixed neutrophils yielded a 195-fold enrichment after five cycles of panning. BstN1 fingerprinting of the enriched library revealed two predominant clones, and DNA sequencing demonstrated highly homologous heavy and light chain variable region segments. Clones were reengineered to express soluble Fab, and neutrophil binding was verified by ELISA. Detailed studies with the two recombinant Fabs, NANUC-1 and -2, validated their identity with serum pANCAs by the criteria of immunofluorescence, confocal microscopy, and DNase I sensitivity. NANUC-1 and -2, like serum UC-pANCA, lack reactivity with previously characterized ANCA-reactive neutrophil proteins and thus detect a novel Ag(s). This study demonstrates the feasibility of selecting phage display Ab libraries on uncharacterized biologic substrates to isolate marker Abs of pathogenic importance.

Amino Acid Sequence↗
PubMed1996

Tumor necrosis factor microsatellites define a Crohn's disease-associated haplotype on chromosome 6.

BACKGROUND & AIMS: HLA class II associations have been described in Crohn's disease (CD) and ulcerative colitis (UC) and may be markers for other closely linked genes that are involved in disease pathogenesis. The tumor necrosis factor (TNF) locus, which contains the genes for TNF-alpha and TNF-beta, is located on chromosome 6 within the major histocompatibility complex loci. To investigate potential genetic associations in inflammatory bowel disease at the TNF locus, we studied 75 patients with CD, 73 patients with UC, and 60 ethnically matched controls using microsatellite markers. METHODS: Five TNF microsatellite loci (TNFa, TNFb, TNFc, TNFd, and TNFe) were typed using polymerase chain reaction. RESULTS: A CD-associated allelic combination, TNFa2b1c2d4e1, was found in 24% of patients with CD, 4.1% of patients with UC (P=0.001; odds ratio, 7.4; CD vs. UC), and 6.7% of control subjects (P=0.01; odds ratio, 4.4 CD vs. controls). This TNF haplotype was associated with the previously described HLA-DR1/DQ5 combination in CD. CONCLUSIONS: The TNFa2b1c2d4e1 allelic combination is the strongest genetic risk factor described in CD and, with HLA class II alleles, defines a group of markers on chromosome 6 that extends from HLA class II to upstream of the TNF-beta gene.

Alleles↗
PubMed1996

Perinuclear antineutrophil cytoplasmic antibodies in patients with Crohn's disease define a clinical subgroup.

BACKGROUND & AIMS: Antineutrophil cytoplasmic antibodies (ANCA) have been consistently detected in a subgroup of patients with Crohn's disease (CD). This study was designed to determine whether serum ANCA expression in patients with CD characterizes an identifiable clinical subgroup. METHODS: The study population consisted of 69 consecutive patients with an established diagnosis of CD as determined by a combination of characteristic clinical, radiographic, endoscopic, and histopathologic criteria. Sera from the patients were analyzed for the presence of ANCAs using the fixed neutrophil enzyme-linked immunosorbent assay (ELISA) assay. Perinuclear ANCA (pANCA)-positive and cytoplasmic ANCA (cANCA)-positive results by ELISA were confirmed by indirect immunofluorescence staining. Clinical profiles of the ANCA-positive patients with CD were compared with those of patients with CD not expressing ANCA (ANCA-negative). RESULTS: pANCA-positive patients with CD have endoscopically and/or histopathologically documented left-sided colitis and symptoms of left-sided colonic inflammation, clinically reflected by rectal bleeding and mucus discharge, urgency, and treatment with topical agents. One hundred percent of patients with CD expressing pANCA had "UC-like" features. CONCLUSIONS: In patients with CD, serum pANCA expression characterizes a UC-like clinical phenotype. Stratification of CD by serum pANCA provides evidence of heterogeneity within CD and suggests a common intestinal mucosal inflammatory process among a definable subgroup of patients with CD and UC expressing this marker.

Adult↗
PubMed1996

Regulation of immune responses of the intestinal mucosa.

The largest lymphoid organ in the body, the intestine, is also the most intriguing and complex. At its root, the gastrointestinal immune system must permit the absorption of nutrients while protecting against invasion of pathogens. In the process, it must sort through vast antigenic challenges and orchestrate an immune response appropriate to the occasion. Whereas the general outline of mucosal immunity has been defined with respect to the phenotype of the immune cells that compose the mucosal immune system, the ontogeny of these immune cells, and the regulation of IgA responses, the details that control mucosal T cell activation and suppression that coordinate this elaborate mucosal network continue to perplex. This review highlights unique aspects of T cell regulation within the intraepithelial lymphocyte (IEL) and lamina propria lymphocyte (LPL) compartments when compared with lymphocytes in the periphery. In general, IEL are largely extrathymically derived, have a limited TCR repertoire capable of recognizing common microbiologic Ags, and demonstrate predominantly cytolytic functions. LPL are thymically derived, highly activated lymphocytes with predominantly Th2 phenotype. LPL activation is distinct from classic memory T cells in their CD2/CD28 predominance that likely contributes to limiting TCR/CD3-mediated signals in the mucosa. Ag presentation in the gut may involve nonclassical, nonpolymorphic class I-like molecules expressed by epithelial cells that may positively select extrathymically derived lymphocyte populations as well as tolerize self-reactive lymphocytes. These special features of the mucosal immune system are integrated to downregulate immune responses to ubiquitous lumenal Ags.

Animals↗
PubMed1996

Association of antineutrophil cytoplasmic antibodies with resistance to treatment of left-sided ulcerative colitis: results of a pilot study.

OBJECTIVE: To determine the frequency of antineutrophil cytoplasmic antibodies with perinuclear staining in patients with treatment-resistant left-sided ulcerative colitis. METHODS: We studied four groups: treatment-resistant left-sided ulcerative colitis, treatment-responsive left-sided ulcerative colitis, ulcerative colitis historical controls, and healthy control subjects. Antineutrophil cytoplasmic antibodies were detected by enzyme-linked immunosorbent assay, and positive results were confirmed by demonstration of a perinuclear staining pattern by indirect immunofluorescence assay. RESULTS: The frequency of perinuclear antineutrophil cytoplasmic antibodies was significantly greater in treatment-resistant left-sided ulcerative colitis (90%) than in treatment-responsive left-sided ulcerative colitis (62%) (P = 0.03) or in ulcerative colitis historical controls (60%). CONCLUSION: The increased frequency of perinuclear antineutrophil cytoplasmic antibodies in treatment-resistant left-sided ulcerative colitis suggests a possible association between these antibodies and relative resistance to medical therapy in patients with ulcerative colitis.

Adolescent↗
PubMed1995

Divergent induction of apoptosis and IL-8 secretion in HT-29 cells in response to TNF-alpha and ligation of Fas antigen.

Colonic epithelial cell injury is the common manifestation of inflammatory diseases of the bowel. One form of epithelial injury is apoptosis. In our study, we investigated the mechanism leading to apoptosis in HT-29 cells in response to TNF-alpha and ligation of Fas Ag. HT-29 displayed a dual response to TNF-alpha and Fas Ag ligation: in combination with IFN-gamma, HT-29 cells underwent apoptosis, whereas independently, these factors stimulated secretion of IL-8. We used this model of immune-mediated epithelial cell injury to elucidate the signals leading to apoptosis in response to TNF-alpha and Fas Ag ligation compared with the signals leading to induction of IL-8 secretion. The model was further used to distinguish signaling differences between TNF-alpha receptors and the Fas Ag in this cell line. The experiments presented here demonstrate that Fas Ag ligation alone led to production of IL-8 by colonic epithelial cells and represented another function mediated by Fas Ag in addition to apoptosis. This study shows that the pathways leading to cell death and IL-8 production in response to Fas Ag ligation and TNF-alpha were similar with regard to their requirements for new gene expression, protein synthesis, and protein kinase activity. Specifically, new gene expression and protein synthesis were not necessary for TNF-alpha- and Fas Ag-mediated apoptosis, but were necessary for TNF-alpha- and Fas Ag-mediated IL-8 secretion. Tyrosine protein kinase phosphorylation was necessary to signal secretion of IL-8 in response to both agonists but it was not necessary for apoptosis. In spite of the similarities between these two agonists, the kinetics of apoptosis via Fas Ag were significantly more rapid than through the TNF-alpha receptor and serve to distinguish these two signals.

Apoptosis↗
PubMed1995

Perinuclear anti-neutrophil cytoplasmic antibodies are spontaneously produced by mucosal B cells of ulcerative colitis patients.

Approximately 60% of sera from ulcerative colitis (UC) patients contains Igs reactive with neutrophil components, raising the question of the origin of these anti-neutrophil cytoplasmic Abs (ANCA). Our assertion that ANCA is a marker for a mucosal disease-related immune response predicts the existence of ANCA producing B cell clones in the lamina propria lymphocyte (LPL) fraction of UC patients. This hypothesis was tested by examining 12-day culture supernatants of LPL ANCA expression. LPL were isolated from surgically removed mucosa from patients with UC, Crohn's disease (CD), and diverticulitis. Normal mucosa was obtained from accident victims or normal margins of colon cancer resections. Supernatants were assayed by a fixed neutrophil ELISA. The ANCA staining pattern of supernatants expressing ANCA, as determined by ELISA, was assessed by indirect immunofluorescent staining of alcohol-fixed neutrophils. ANCA was found in 70% of culture supernatants from UC LPL fractions. In contrast, only approximately 11% of supernatants from CD and diverticulitis/normal (noninflammatory bowel disease (IBD)) LPL displayed ANCA binding. A perinuclear (pANCA) staining pattern was obtained with 70% of ANCA-expressing UC LPL supernatants, whereas ANCA-expressing CD and non-IBD LPL supernatants displayed a cytoplasmic reaction. PBL and mesenteric lymph node lymphocytes lacked spontaneous pANCA production, and pANCA production from PBL was not inducible. These findings indicate the existence of pANCA-producing B cell clones in mucosal lesions of UC patients and support our hypothesis that pANCA production is a consequence of a mucosal immune response specific to UC.

Autoantibodies↗
PubMed1995

Definition of a lamina propria T cell responsive state. Enhanced cytokine responsiveness of T cells stimulated through the CD2 pathway.

This study was designed to compare cytokine release in lamina propria lymphocytes (LPLs) and PBLs activated by Abs against CD3, CD2, and CD28. LPL T cells were significantly more responsive to CD2 ligation than PBL, as determined by release of IFN-gamma, IL-2, IL-4, and TNF-alpha. Moreover, CD28 co-ligation in LPLs exaggerated CD2 > CD3 dominance in cytokine induction. PHA-activated PBLs expressed more CD2 receptors than freshly isolated LPLs, but were less responsive to activation through CD2, indicating that postreceptor pathways in LPL may be adapted specifically to facilitate CD2-mediated cytokine secretion. Antiphosphotyrosine (APT) immunoblotting revealed inducible substrate phosphorylation during CD2, but not CD3, ligation in whole LPLs, as well as LPL-derived T cell lines. PBLs cocultured with an irradiated B cell line, Daudi, and IL-2 for 5 days attained a CD2-dominant cytokine-secretion pattern with identical tyrosine phosphorylation profiles as freshly isolated LPL or LPL T cell lines. PHA-activated PBLs did not produce these tyrosine phosphorylation profiles. This suggests that B lymphocytes in the lamina propria may contribute to a T cell differentiation process in which CD2, possibly by potentiation of its postreceptor pathway, becomes a prominent receptor for induction of cytokine secretion.

Animals↗
PubMed1995

Morbidity of subtotal colectomy in patients with severe ulcerative colitis unresponsive to cyclosporin.

PURPOSE: The aim of this study was to document the morbidity of urgent subtotal colectomy and ileostomy in patients with severe ulcerative colitis who failed cyclosporin treatment. METHODS: We reviewed the charts of patients with severe ulcerative colitis who did not respond to cyclosporin treatment and underwent urgent subtotal colectomy and Brooke ileostomy at two inflammatory bowel disease centers over the 12-month period ending April 1994. RESULTS: Fourteen patients (6 males; mean age, 34 years) required an urgent subtotal colectomy and Brooke ileostomy after failing treatment with cyclosporin. There were no deaths. Eight patients (57 percent) developed post-operative complications, which included ileus (3), deep vein thrombosis (2), wound infection (2), and partial dehiscence of rectal stump (1). Mean length of postoperative hospital stay was 8.8 days. CONCLUSIONS: These initial data suggest that cyclosporin treatment may not influence the safety of urgent surgical treatment in severe ulcerative colitis.

Adolescent↗
PubMed1995

High-titer antineutrophil cytoplasmic antibodies in type-1 autoimmune hepatitis.

BACKGROUND/AIMS: Autoimmune hepatitis (AIH), an unresolving liver inflammation characterized by periportal hepatitis and presence of serum autoantibodies, is distinguished by smooth muscle antibody and/or antinuclear antibody seropositivity. Type-2 AIH is characterized by antibodies to liver/kidney microsome type-1. Antineutrophil cytoplasmic antibodies (ANCAs) are highly specific for ulcerative colitis, primary sclerosing cholangitis, and, in this report, type-1 AIH determined by positive enzyme-linked immunosorbent assay confirmed by perinuclear indirect immunofluorescence staining. The studies described characterize the frequency and nature of ANCA in severe type-1 AIH patients and define AIH-ANCA specificity and diagnostic significance. METHODS: One hundred four patients, characterized by clinical, immunoserological, virological, histological, and antigenic criteria, were studied. ANCA expression was assayed by enzyme-linked immunosorbent assay. RESULTS: High-titer ANCA is present in 96% of patients with type-1 AIH with 92% showing a perinuclear staining pattern (pANCA). Whereas many patients were seropositive for antinuclear antibodies, the titer of ANCA did not correlate with the titer of antinuclear antibodies. ANCA expression did not correlate with the presence or absence of other autoimmune disorders. Finally, 80% of patients with AIH examined expressed only immunoglobulin G1 pANCA contrasting with the 33% of patients with PSC with pANCA subclass specificity. CONCLUSIONS: The presence of ANCA seems to be an independent and selective marker for type-1 AIH.

Adolescent↗
PubMed1995

Intercellular adhesion molecule 1 gene associations with immunologic subsets of inflammatory bowel disease.

BACKGROUND & AIMS: Inflammatory bowel disease is characterized by a failure to down-regulate the usual self-limited gut inflammatory response, suggesting that one or more of the predisposing genes could be those that determine the level of the immune response along the inflammatory pathway. The aim of this study was to examine potential associations of intercellular adhesion molecule 1 (ICAM-1) gene polymorphisms with inflammatory bowel disease or subsets of inflammatory bowel disease. METHODS: One hundred eighteen patients with ulcerative colitis (UC) and 130 patients with Crohn's disease (CD) as well as 77 ethnically matched controls were tested for antineutrophil cytoplasmic antibodies (ANCAs) and genotyped by polymerase chain reaction and allele-specific oligonucleotide techniques for ICAM-1 polymorphisms at codon 241 (exon 4) and codon 469 (exon 6). RESULTS: There was no significant difference between all patients with UC, patients with CD, and controls in either polymorphism. However, when stratified by ANCA status, ANCA-negative UC showed a significantly increased frequency of allele R241 compared with ANCA-positive UC (16.0% vs. 6.6%; P = 0.047, Fisher's Exact Test). In contrast, it was ANCA-positive CD that had an increased allele frequency compared with ANCA-negative CD (19.6% vs. 8.4%; P = 0.027, Fisher's Exact Test). CONCLUSIONS: Because the codon 241 polymorphism is in a functionally important domain III of ICAM-1, we may have identified an actual responsible genetic variation for genetically heterogeneous subsets of both UC and CD.

Alleles↗
PubMed1995

Role of antineutrophil cytoplasmic antibodies in an ethnically distinct population: Korean patients with ulcerative colitis.

OBJECTIVES: Studies have suggested that antineutrophil cytoplasmic antibodies (ANCA), known as a useful diagnostic marker in patients with ulcerative colitis (UC), may have a genetic basis, particularly in association with HLA class II genes. Because most studies examining the role of ANCA in UC have been performed in ethnically undefined populations, we have analyzed ANCA status in an ethnically distinct group of patients with UC. METHODS: Serum samples from 24 Korean patients with a known diagnosis of UC and 58 healthy Koreans were examined for the presence of ANCA, using a fixed neutrophil enzyme-linked immunosorbent assay. ANCA-binding patterns were examined by indirect immunofluorescence. RESULTS: The incidence of ANCA in 83.3% of Korean patients with UC was significantly higher than in controls (p < 0.0001). The mean binding level at a 1:100 dilution and the titer of ANCA were significantly higher in patients with UC than in controls. Among UC patients with ANCA, there was also a high incidence of perinuclear binding pattern. In contrast, there was no relationship between ANCA and age of patients, duration, activity, or extent of disease. CONCLUSIONS: High sensitivity and specificity of ANCA in an ethnically distinct group of patients with UC show that ANCA expression may not be ethnically determined, and they confirm the utility of ANCA as a useful diagnostic indicator of UC in an ethnically diverse groups of patients.

Adult↗
PubMed1995

Antineutrophil cytoplasmic antibody correlates with chronic pouchitis after ileal pouch-anal anastomosis.

BACKGROUND: Perinuclear antineutrophil cytoplasmic antibodies, present in 60% of patients with ulcerative colitis, may be a marker for a genetically distinct subset of patients who develop chronic pouchitis after undergoing ileal pouch-anal anastomosis. The frequency of these antibodies in chronic pouchitis was determined. METHODS: Four groups were studied: patients who underwent ileal pouch-anal anastomosis for colitis with and without chronic pouchitis, familial polyposis without pouchitis and ileostomy for colitis. Antineutrophil cytoplasmic antibody levels and titers were detected by ELISA, and positive results were confirmed by perinuclear staining with indirect immunofluorescence. RESULTS: The frequency of perinuclear antineutrophil cytoplasmic antibodies in chronic pouchitis (100%) was significantly greater than in colitis (50%) or familial polyposis (0%) without pouchitis and colitis with an ileostomy (70%); p = 0.00, 0.00, and 0.01, respectively. CONCLUSIONS: The finding that perinuclear antineutrophil cytoplasmic antibodies occur more frequently in patients with chronic pouchitis raises the possibility that this antibody may mark a genetically distinct subset of ulcerative colitis patients. Further studies are needed to determine whether the presence of this antibody before ileal pouch-anal anastomosis is predictive for later development of chronic pouchitis.

Adenomatous Polyposis Coli↗