Investigation on lymphocyte subpopulations in the intestinal lamina propria in inflammatory bowel diseases.

Intestinal lamina proprial lymphocytes were enumerated in 13 patients with Crohn's disease (CD), 7 with ulcerative colitis (UC) and 9 control subjects with grossly normal bowel. The percentages and absolute numbers of B cells and complement receptor-bearing lymphocytes in the patients with UC did not differ significantly from those of the control group; but in CD, the percentages of these cells were significantly decreased despite that the absolute numbers were normal. The percentages and absolute numbers of T cells identified by E rosettes (regular and stable) were normal in both CD and UC. In both diseases, significantly increased percentages but normal absolute numbers of mature T cells were identified by monoclonal antibody staining with the CD3 reagent. There was an increased proportion of suppressor/cytotoxic T cells and a concomitant significant decrease of the helper to suppressor T-cell ratio (using either percentages or absolute numbers of cells) in tissues from patients with CD, but not with UC as compared with the control group. These results suggest that the imbalance of T-cell subpopulations in the intestinal lamina propria may play a role in the pathogenesis of CD.

D-lactate-associated encephalopathy after massive small-bowel resection.

D-Lactate-associated encephalopathy is a rare clinical syndrome characterized by dizziness, ataxia, confusion, headaches, memory loss, lethargy, and aggressiveness which may progress to frank but reversible coma. It occurs in patients with profound dysfunction of the short-bowel syndrome and is believed to result from massive carbohydrate malabsorption with resultant over-production of D-lactate and other organic anions by the colonic flora. Extremely elevated serum levels of D-lactate (but not L-lactate) confirm the diagnosis, but currently D-lactate is not clearly established as the putative neurotoxin. We describe a patient who repeatedly developed D-lactate encephalopathy after surgical removal of nearly the entire jejunum and ileum. Markedly elevated D-lactate serum levels were documented during an encephalopathic episode. Potential pathophysiologic mechanisms and the treatment rationale are discussed.

Modern clinical aspects of inflammatory bowel disease.

Ulcerative colitis and Crohn's disease are idiopathic conditions that represent an overlapping clinical spectrum that is commonly referred to as inflammatory bowel disease (IBD). Among the etiopathogenic hypotheses that have been suggested, infectious, genetic, and immunologic factors have received the most attention in the modern era--sometimes in combination. This article discusses current concepts regarding the etiology, demographics, and general clinical characteristics of IBD. The latter discussion covers signs/symptoms, laboratory abnormalities, and endoscopic findings.

Staphylococcal protein A bound to Sepharose 4B is mitogenic for T cells but not B cells from rabbit tissues.

The mitogenicity of protein A from Staphylococcus aureus bound to Sepharose 4B (SpA-S) was tested against mononuclear cells from normal rabbit spleens and Peyer's patches after using Sephadex G-10 adherence chromatography to deplete macrophages and Sephadex G-200 anti-rabbit F(ab')2 immunoabsorbent columns to obtain B-enriched lymphocytes. Macrophage-depleted unseparated lymphocytes and the B-cell-depleted (T-cell-enriched) fractions from both tissues consistently showed good mitogenic responses to SpA-S. In contrast, the B-cell-enriched populations from either tissue did not respond to SpA-S. Supplementary experiments employing glass adherence and T-cell autorosetting did not support the possibility that the more efficient immunoabsorbent method of B-cell isolation had in some way caused the unresponsiveness to SpA-S. These results indicate that SpA-S is mitogenic for rabbit tissue T cells but will not serve as a T-independent mitogen for rabbit tissue B cells.

Circulating lymphocyte subpopulations in Crohn's disease.

Circulating lymphocytes were enumerated in 28 patients with Crohn's disease and in 12 patients with other diseases by rosetting and by immunofluorescent staining using monoclonal antibodies for T-cell surface phenotypic markers [OKT3 (mature), OKT4 (helper), and OKT8 (suppressor/cytotoxic)] or polyvalent antisera for surface immunoglobulins (B cells). Total lymphocyte counts were reduced only in those with non-steroid-treated active Crohn's disease. Circulating monocyte counts, proportions of peripheral T and B cells, and percentages and absolute numbers of mature, helper, and suppressor T-cell subclasses in Crohn's disease were not significantly different than in the controls. Helper to suppressor T-cell ratios were comparable in all subjects, varying directly with numbers of helper T cells (p less than 0.05). Individual ratios of helper to suppressor T cells did not correlate with disease activity or location, the use of steroids, serum albumin, or total lymphocyte or monocyte counts. This study provides no evidence for underlying abnormalities of circulating lymphocyte subpopulations in Crohn's disease when compared to subjects with other illnesses. The characterization of lymphocyte subclasses in affected tissues is an important area of continuing investigation.

Inflammatory tissue reaction in rabbit bowel injected with Crohn's homogenates.

Homogenates from the terminal ileum of a patient with Crohn's disease with granulomas were prepared as snap-frozen or fresh and were injected into the ascending colonic walls of New Zealand white rabbits. Control animals were injected with 1 per cent bovine serum albumin alone. The rabbit bowel was examined after 1 year, and lesions were noted in each of the rabbits injected with Crohn's disease homogenate, irrespective of the type of tissue preparation. The observed lesions were diffuse and occurred both at the injection site and in the terminal ileum. These changes were not noted in the control group. This work confirms earlier results in the same animal model and suggests that either fresh or snap-frozen homogenates will produce the intestinal lesion but that bovine albumin alone will not.

Antimitochondrial antibodies: reagent variables may lead to diagnostic error.

Laboratory-prepared and commercially obtained fluorescein-labeled rabbit antihuman IgG were compared in performing the antimitochondria antibody (AMA) assay. Identical results were obtained using either of the fluorescent antisera at protein concentrations of 1.5 mg/ml and 1:10 dilutions of patients' sera. Positive AMA tests with either antisera were observed in each of 7 patients with primary biliary cirrhosis (PBC), 2 of 83 patients with miscellaneous hepatic diseases, and in 1 of 24 patients with extrahepatic biliary obstruction (EBO) of 2-24 weeks duration. However, when undiluted commercial fluorescent antiserum (15.8 mg protein/ml) was substituted in the assay, sera from 11 of 23 AMA-negative patients with EBO and 12 of 15 with miscellaneous liver diseases demonstrated an atypical fluorescence located primarily along the periphery of the rat renal tubules. Thus, if the conjugated antibody is not adjusted to an optimal protein concentration, this atypical fluorescence could be interpreted as a positive AMA test and lead to diagnostic error.

Inherited deficiency of second component of complement and HLA haplotype A10,B18 associated with inflammatory bowel disease.

A patient with inflammatory bowel disease and sacroiliitis had haplotypes A10,B18 and Aw32,b18 at the major histocompatibility locus. Serum total complement and C2 hemolytic complement activities were undetectable; levels of the remaining C1-C9 components were normal. The parents, both siblings, and a child each had half-normal levels of C2 and either the A10,B18 or the Aw32,b18 hla haplotype. In a second unrelated family, an only child and both parents developed inflammatory bowel disease. The father and child had HLA haplotype A10,B18, but, along with the mother, each had normal serum levels of hemolytic C and C2. Homozygous C2 deficiency, often in association with the A10,B18 haplotype, has previously been linked with various autoimmune diseases and with propensity to infection. Our findings suggest that C2 deficiency or this haplotype also may predispose to inflammatory diseases of the intestine.

The production of an unusual tissue reaction in rabbit bowel injected with Crohn's disease homogenates.

Recent reports have suggested a transmissible factor in the etiology of Crohn's disease, which had yet to be confirmed. The specificity of the transmission was tested with a disease control of ulcerative colitis as well as normal bowel. Twenty New Zealand White rabbits received inoculum of tissue homogenates from the terminal ileum of normal, ulcerative colitic, and Crohn's disease patients. This inoculum was injected into the wall of the ascending colon and the animals were examined after one year. Changes were noted consistently only in those animals receiving the Crohn's disease inoculum. These changes consisted of thickened bowel wall with increased mucosal folds, thickened mesenteric fat with some creeping, irregular areas of thin colonic mucosa, and hyperplastic mesenteric lymph nodes. The terminal ileum distant from the inoculum site was smooth with atrophic changes only in the Crohn's inoculated group of animals. These animals also had discrete collections of macrophages in colon or sacculus, mucosal and submucosal edema, and chronic inflammation of the colon. However, the characteristic features of Crohn's disease were not reproduced.

Inflammatory bowel disease in all three members of one family.

The occurrence of inflammatory bowel disease in all three members of one family is described. Studies of white blood cell chromosomes, histocompatibility antigens, and cellular and humoral immunity failed to explain this unusual phenomenon. However, the appearance of inflammatory bowel disease in an entire family reemphasizes the potential role of genetic and environmental influences in the pathogenesis of some cases of ulcerative colitis and Crohn's disease.

Unexplained bronchopulmonary disease with inflammatory bowel disease.

Six patients developed severe, unexplained, chronic bronchopulmonary disease from 3 to 13 years after the onset of nonspecific inflammatory disease of the colon. All had chronic bronchitis, bronchiectasis was diagnosed in four, and an obstructive type of pulmonary dysfunction was noted in five. Four of the six, including the two with only chronic bronchitis, had no history of smoking. There was an initial correlation between the pulmonary symptoms and the intestinal disease, except in two patients who developed overt pulmonary disease following total proctocolectomy. The frequent occurence of extraintestinal lesions has suggested that ulcerative colitis and regional enteritis are systemic disorders. Chronic unexplained bronchopulmonary disease may be another infrequent complication in such patients.

Alteration of T cell function in healthy persons with a history of thymic x-irradiation.

The possible late effects of x-irradiation to the infantile thymus were investigated by studying immune functions in 12 healthy persons with a history of thymic x-irradiation and healthy control subjects. No differences were found in serum immunoglobulin values, humoral antibody levels, lymphocyte counts, and lymphocyte reactivity to phytochemagglutinin, vaccinia virus, purified protein derivative (PPD), and allogeneic cells. The irradiation group exhibited cellular hyperresponsiveness to streptoskinase-streptodornase (SK-SD). In contrast, mean skin and in vitro lymphocyte responses to Candida albicans were depressed in the patients with thymic irradiation. A dissociation of these two Candida responses was found in only 1 of 14 healthy control subjects but in 7 of 12 irradiated individuals. While thymic irradiation did not result in impaired immunologic defenses leading to clinical disease, it caused alterations in T cell responses similar to those reported in patients with chronic mucocutaneous candidiasis.