Sumner C. Kraft

Distribution of Immunoglobulins in Human Rectal Mucosa: I. Normal control subjects

Summary Eight normal subjects were studied utilizing a simplified technique for determining the number of pyroninophilic and immunoglobulin-containing cells per unit area of interstitial tissue in the rectal mucosa. Histologically normal proctoscopic biopsy sections were stained with methyl greenpyronin and fluorescein-labeled monospecific antisera against various human immunoglobulins. Cell density indices for pyroninophilic cells exceeded the sum of the cell density indices for immunoglobulin cells in each subject. IgA-containing cells predominated over IgM, IgG, and IgD cells. These quantitative histological and immunohistochemical data provide normal values for continuing studies of local immunological processes in the normal and diseased gastrointestinal tract. In addition, IgA repeatedly was identified within the apical portion of the cytoplasm of epithelial cells of rectal mucosal glands. The predominance of IgA in gastrointestinal tissues and secretions and the finding of intraepithelial cell IgA support the concept of a unique type of local IgA system, the biological importance of which remains unknown.

Distribution of Immunoglobulins in Human Rectal Mucosa: II. Ulcerative colitis and abnormal mucosal control subjects

Summary This study endeavored to identify and quantitate the major classes of immunoglobulins in rectal mucosal biopsies from 9 adults with quiescent or mildly active ulcerative colitis and 7 abnormal mucosal control subjects. Serial cryostat-cut tissue sections were stained with hematoxylin-eosin, methyl green-pyronin, and fluorescein-conjugated monospecific antisera to human serum immunoglobulins. As in normal and abnormal control subjects, IgA was demonstrated within the apical portion of the cytoplasm of rectal mucosal epithelial cells in all ulcerative colitis tissues. Although IgA cells predominated over IgM-, IgG-, and IgD-containing cells, the population density of IgA cells in the lamina propria of the rectal mucosa in ulcerative colitis was lower than in normal rectal tissues. Unlike control subjects, in ulcerative colitis IgA commonly was present in extracellular interstitial mucosal sites and IgA-containing cells were distributed irregularly and some fields showed very few IgA cells. The mean number of IgG cells per unit area of mucosal interstitium also was reduced in ulcerative colitis rectal tissues. The ulcerative colitis patients and the two control groups showed no staining differences for IgM and IgD.

Circulating lymphocyte subpopulations in Crohn's disease

Circulating lymphocytes were enumerated in 28 patients with Crohns 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 Crohns 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 Crohns 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 Crohns disease when compared to subjects with other illnesses. The characterization of lymphocyte subclasses in affected tissues is an important area of continuing investigation.

Immunoglobulin A: Localization in Rectal Mucosal Epithelial Cells

Immunofluorescence studies with monospecific antiserums to human serum immunoglobulins consistently revealed immunoglobulin A within the apical portion of the cytoplasm of rectal mucosal epithelial cells in normal subjects, as well as in patients with various bowel diseases. Immunoglobulins M, G, and D were not demonstrated within mucosal epithelial cells. The predominance of lymphoid cells containing immunoglobulin A in the lamina propria of intestinal tissues was confirmed.

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.

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 Crohns disease.

Intestinal Malabsorption and Immunoglobulin Deficiency

Available evidence suggests that hypogammaglobulinemia, particularly immunoglobulin A (IgA) deficiency, may be associated with intestinal malabsorption and mild to moderate villous atrophy of the proximal jejunal mucosa.1-3We have encountered such a patient who responded favorably in turn to a gluten-free diet and to tetracycline hydrochloride therapy administered orally. The purpose of this report is to relate the clinical and immunological findings in this case to published data from other patients with malabsorption and documented immunoglobulin deficiencies. Methods For Special Studies The serological and tissue techniques, as well as the method used to quantify mucosal lymphoid cells employing cell density indices (CDI), have been reported.4The CDI are arbitrary units which represent cells per unit area of interstitium.4In the previous study of eight specimens of normal human rectal mucosa, the CDI (mean ± SE of the mean) for IgA-, IgM- and IgG-containing lymphoid cells were 80.14

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.

Humoral and cellular responses to native antigen following oral and parenteral immunization with lipid-conjugated bovine serum albumin

Abstract Humoral and cellular immune responses of rabbits to bovine serum albumin (BSA) were measured following oral and parenteral immunization with either BSA or one of two dodecanoic acid conjugates of BSA. The first consisted of a mixture of lightly and heavily conjugated BSA-molecules (L-BSA-mix), while the second (L-BSA) was a homogeneous preparation of heavily conjugated BSA with more than 95% of the 60 available amino groups covalently bound to dodecanoic acid. Animals ingesting L-BSA-mix had a similar humoral immune response but enhanced cellular reactivity to BSA in comparison to animals ingesting the native antigen. No systemic immunologic responses to BSA were detected following ingestion of L-BSA in spite of the demonstration of circulating BSA antigenic groups. This lack of a detectable immune response after oral administration was not due to masking of antigenic sites by the lipid residues since both humoral and cellular immune responses to BSA were obtained in animals injected with L-BSA. Ingestion of L-BSA did not induce tolerance since a subsequent injection of BSA elicited a normal primary immune response. The differences in immunogenicity between BSA, L-BSA and L-BSA-mix following oral administration may be related to different modes of antigen recognition by the gut-associated lymphoid tissues.

Crohn's Disease of the Mouth

Excerpt Crohns disease was first observed in the terminal ileum, but has since been shown capable of involving any part of the gastrointestinal tract from the mouth to the anus. It is well known t...