Evidence for Chlamydia in Crohns Disease

Abstract

Chlamydia cause enteritis in young pigs and calves, and granulomas within intestinal lymphatics. Recently we called attention to the lymphangitis and lymphatic obstruction that occurs in Crohn's disease. We searched resected tissues from patients for evidence of chlamydia and sera for evidence of previous exposure to chlamydia. Immunohistochemistry and real-time PCR were employed to seek chlamydia in preserved tissues. In the IHC, antibody to C. trachomatis served as primary antibody; in the PCR, primers specific for Chlamydiaceae were employed. Commercial ELISA kits measured anti-chlamydia IgG and IgA against C. trachomatis antigen in sera derived from a population of patients different from that which yielded the tissue specimens. IHC revealed focal positive staining for chlamydia in tissues of 5 of 19 patients. Positive reacting cells occurred within dense inflammation, in sparsely scattered macrophages in the submucosa and subserosa. Tissues from 3 of 22 control subjects were positive. Real-time PCR done on ileal, colonic, and regional lymph node tissues revealed evidence of chlamydia in 3 of 33 patients. Serology for anti-chlamydia IgG revealed 2 positive values in 24 patients, while serology for anti-chlamydia IgA revealed 4 positives among the 24 patients, and 1 positive in the 15 controls. One patient and one control had both elevated IgG and IgA titers. The 4 patients with elevated IgA titers were from a single family of 6 with Crohn's disease, which had been previously described. Additional consideration needs to be given to the chlamydia species, including those of animal origin, which leave behind little evidence of their previous involvement.

ELISA Serology for Antibodies Against Chlamydia trachomatis in Crohn’s Disease

“…On the other hand, though not attaining statistical significance, the data appear to show that familial CD patients have had greater exposure to Chlamydia antigen than sporadic CD patients, which supports our earlier results with one family from the north of France (in the latter instance, in IgA levels) [ 4 ]. If the difference is real, what possible reasons might explain the increased number of positives in familial disease?…”

“…At first glance, our data ( Table 2 [ 4 - 15 ]) appear to show no serologic relationship between C. trachomatis and CD. This finding, of a lack of or little antibody response in CD patients, agrees with Rodaniche et al [ 5 ], Swarbrick et al [ 6 ], Taylor-Robinson et al [ 7 ], Elliot et al [ 8 ] and McGarity et al [ 9 ] of previous studies done by other methods, and it disagrees with Schuller et al [ 10 ], Mardh et al [ 11 ], Gump et al [ 12 ] and Orda et al [ 13 ].…”

“…Searching for microbes that might damage lymphatic endothelium and in particular the endothelium of intestinal lymphatics, we discovered the importance of an infectious pig model of CD, in animals inoculated with Chlamydia suis [ 3 ]. As a consequence, evidence for Chlamydia in the resected tissues of patients and antibodies against this microorganism were sought [ 4 ].…”

“…Employing commercial enzyme-linked immunosorbent assay (ELISA) kits for Chlamydia trachomatis , serology for anti- Chlamydia IgG revealed two positive values in 24 patients, versus one positive among 15 controls, while serology for anti- Chlamydia IgA revealed four positives among the 24 patients, and one positive in 15 controls [ 4 ]. One patient and one control had both elevated IgG and IgA titers.…”

“…One patient and one control had both elevated IgG and IgA titers. The four patients with elevated IgA titers were from a single family of six, all of whom had CD [ 4 ]. In an attempt to test the importance of positive serology, we investigated 323 sera from patients registered with an inflammatory bowel disease (IBD) center in northern France, as well as 74 control sera from the same region.…”