The leukocyte count predicts the efficacy of treatment with azathioprine in inflammatory bowel disease.

INTRODUCTION: Azathioprine has variable efficacy in inflammatory bowel disease. Previous studies suggested that either neutropenia, an increase in the mean corpuscular volume, the assessment of thiopurine methyl-transferase activity or erythrocyte 6-thioguanine values might predict the treatment response. However, due to the conflicting results of the preceding studies there are yet no established laboratory values which allow an estimation of the clinical response. PATIENTS AND METHODS: 45 patients with Crohn's disease and 39 patients with ulcerative colitis were enrolled in this retrospective evaluation. After a minimum of six months therapy with azathioprine patients in remission were compared with those who did not achieve a stable remission with respect to the number of leucocytes, lymphocytes, neutrophil granulocytes and the mean corpuscular volume. RESULTS: Patients who went into remission during treatment with azathioprine displayed significantly lower leukocyte counts if compared to patients who were not in remission (p = 0.004 in Crohn's disease and 0.003 in ulcerative colitis). A similar tendency was also observed with respect to the granulocyte count (p = 0.007 in Crohn's disease and 0.004 in ulcerative colitis). The mean corpuscular volume did not correlate with the response to purine analogues. DISCUSSION: The absolute leukocyte count and the percentage of granulocytes seem to predict the response to purine analogues in inflammatory bowel disease and possibly offers a feasible and cost effective diagnostic tool for the assessment of therapeutic efficacy. Subsequent preferably prospective studies should aim to define the optimal cut-off value for the leukocyte count.

A645G (Lys216Glu) polymorphism of the bactericidal/permeability-increasing protein gene in periodontal disease.

Bactericidal/permeability-increasing protein (BPI) is a member of the pattern recognition receptors of the innate immune system and recognizes lipopolysaccharides (LPS), a bacterial component belonging to the pathogen-associated molecular patterns (PAMPs). BPI mediates the neutralization of LPS and increases the phagocytosis and cytotoxicity against bacteria. Recently, the functionally effective polymorphism A645G resulting in the amino acid alteration Lys216Glu has been described. The aim of the study was to investigate the association of the A645G polymorphism with chronic periodontal disease. The study population comprised 123 patients with periodontal disease (36 with mild, 52 with moderate and 35 with severe periodontitis) and 122 healthy, unrelated control individuals. Genotyping of the BPI gene polymorphism A645G (Lys216Glu) was performed by polymerase chain reaction and restriction fragment length polymorphism analysis. Statistical analysis was carried out employing the chi(2) test with Yates correction. Genotype and allele frequencies of the polymorphism tested herein showed no significant differences between periodontal disease as compared to the control group. The frequencies of the G allele were 52.4% in patients with periodontal disease and 49.2% in the control individuals (P = 0.528). Moreover, no significant associations could be detected after stratification for disease severity and according to gender. The present study does not give evidence for the contribution of the BPI gene to the genetic background of chronic periodontal disease.

Prevalence of the -295 T-to-C promoter polymorphism of the interleukin (IL)-16 gene in periodontitis.

Interleukin (IL)-16 is involved in the regulation of the expression of several proinflammatory cytokines, i.e. tumour necrosis factor (TNF)alpha and interleukin (IL)-1beta. The present study aimed to determine the prevalence of the -295 promoter polymorphism of the interleukin (IL)-16 gene in periodontal disease. A total of 123 patients with periodontal disease and 122 healthy controls were genotyped for the -295 IL-16 promoter polymorphism. Genotyping has been performed by PCR and restriction fragment length polymorphism (RFLP) analysis. The frequencies of alleles and genotypes as well of haplotypes within both study groups were compared using the Pearson chi(2) test at a level of significance of 5% (P < 0.05). The distribution of genotypes for the -295 IL-16 gene polymorphism showed no significant difference between periodontitis patients and healthy control subjects (P = 0.886). Also stratification analysis according to the disease severity revealed no significant difference regarding the genotype distribution among both study groups. Herein the IL-16 -295 gene polymorphism was not associated with chronic periodontitis.

Serum antibodies in first-degree relatives of patients with IBD: a marker of disease susceptibility? A follow-up pilot-study after 7 years.

INTRODUCTION: Various disease-specific serum antibodies were described in patients with inflammatory bowel disease and their yet healthy first-degree relatives. In the latter, serum antibodies are commonly regarded as potential markers of disease susceptibility. The present long-term follow-up study evaluated the fate of antibody-positive first-degree relatives. PATIENTS AND METHODS: 25 patients with Crohn's disease, 19 patients with ulcerative colitis and 102 first-degree relatives in whom presence of ASCA, pANCA, pancreatic- and goblet-cell antibodies had been assessed were enrolled. The number of incident cases with inflammatory bowel disease was compared between antibody-positive and antibody-negative first-degree relatives 7 years after storage of serum samples. RESULTS: 34 of 102 (33%) first-degree relatives were positive for at least one of the studied serum antibodies. In the group of first-degree relatives, one case of Crohn's disease and one case of ulcerative colitis were diagnosed during the follow-up period. However, both relatives did not display any of the investigated serum antibodies (p=1). DISCUSSION: The findings of our pilot study argue against a role of serum antibodies as a marker of disease susceptibility in first-degree relatives of patients with inflammatory bowel disease. However, these data have to await confirmation in larger ideally prospective multicenter studies before definite conclusions can be drawn.

Polymorphisms in the DLG5 and OCTN cation transporter genes in Crohn's disease.

BACKGROUND AND AIMS: Recent data suggest identification of causal genetic variants for inflammatory bowel disease in the DLG5 gene and in the organic cation transporter (OCTN) cluster, both situated in previously described linkage regions. PATIENTS AND METHODS: The polymorphisms in DLG5 (113 G-->A, 4136 C-->A, and DLG5_e26), SLC22A4 (1672 C-->T), and SLC22A5 (-207 G-->C) were assessed in 625 patients with Crohn's disease (CD), 363 patients with ulcerative colitis (UC), and 1012 healthy controls. Association with disease susceptibility, clinical phenotypes, and possible genetic interactions of these polymorphisms with disease associated CARD15/NOD2 mutations was analysed. RESULTS: No significant association of DLG5 polymorphisms with CD or UC was observed. Homozygosity for the OCTN-TC haplotype was associated with an increased CD risk (OR = 1.65), which was even greater in the presence of CARD15 mutations. Genotype-phenotype analysis revealed that this association was particularly strong in patients with colonic disease. The TC haplotype was associated with non-fistulising non-fibrostenotic disease, an earlier age of disease onset, and reduced need for surgery. CONCLUSION: Our observations argue against a role of DLG5 polymorphisms in the susceptibility for inflammatory bowel disease, whereas the OCTN polymorphisms are associated with CD. However, due to the comparable weak association observed herein, extended linkage disequilibrium analyses of these variants with the IBD5 haplotype tagged single nucleotide polymorphims might be advisable before definitive conclusions about their causative role in CD can be drawn.

No significant association between mutations in exons 6 and 8 of the autoimmune regulator (AIRE) gene and inflammatory bowel disease.

Various autoantibodies have been described in patients with inflammatory bowel disease. The autoimmune regulator (AIRE) functions as a transcription factor in cells responsible for the induction and maintenance of immunological tolerance. In contrast to classic autoimmune disorders, polymorphisms of the AIRE gene are not associated with inflammatory bowel disease, despite the presence of disease-specific autoantibodies.