Non-autoimmune Diseases Research Articles

T cell antigen receptors in autoimmunity.

Three mAb to variable region determinants of the alpha/beta-chain TCR were used to detect discrete populations of peripheral blood T cells. T cells sharing a TCR determinant defined by such an antibody presumably use the same or similar TCR V or J genes for their alpha- or beta-chains. Thus analysis with these mAb provides a tool to investigate TCR gene usage and expression. Since autoantigen specific T cells may play an important role in initiating autoimmune diseases, TCR were analyzed in different autoimmune diseases and control groups including rheumatoid arthritis, Graves disease, idiopathic thrombocytopenic purpura, psoriasis, SLE, insulin-dependent diabetes mellitus, and in nonautoimmune control diseases and normals. Purified T cells were stained by indirect immunofluorescence with three mAb to TCR variable regions: mAb S511 stains 1.8 +/- 0.9% (mean +/- 2 SD), mAb C37 stains 3.4 +/- 1.5% and mAb OT145 stains from 0 to 6% of T cells from normal donors. Several individuals were identified with expanded subsets of positive T cells. One patient with adult ITP followed during a 12-mo period consistently had elevated percentages of T cells staining with the mAb OT145 (15.9 to 24.5%). These cells were found to be exclusively CD8+. By Southern blotting DNA prepared from these OT145+, CD8+ cells, but not DNA from the patient's OT145- T cells, revealed a clonal rearrangement using a beta-chain C region probe. Thus this patient had a monoclonal expansion of CD8+, OT145+ cells. Hyperexpression of a TCR variable region, as defined by the available mAb, could not be associated with any of the diseases studied. Examination of T cells at the site of autoimmunity, such as T cells from rheumatoid arthritis synovial fluid, revealed normal percentages of cells staining with these mAb. Immunoperoxidase staining of psoriatic lesional skin showed no striking enrichment of T cells bearing one or the other TCR type.

Autoantibodies to extracellular collagen matrix components in epidermolysis bullosa and other bullous diseases

In order to determine whether autoantibodies are present in sera from normal individuals and/or patients with selected bullous disorders, a highly sensitive solid-phase radioimmune assay was established using purified native collagen types I-VI, laminin, and fibronectin as substrates. Sixty-four sera were utilized, representing 12 normal controls as well as 4 patients with extensive thermal burns, 18 with autoimmune bullous diseases (11 bullous pemphigoid, 5 pemphigus vulgaris, and 2 epidermolysis bullosa acquisita), and 30 with non-autoimmune mechanobullous diseases [epidermolysis bullosa (EB): 20 simplex, 4 junctional, and 6 dystrophic]. In general, autoantibodies to types I, II and VI collagen and fibronectin were undetectable in any of the patient or control groups. In contrast, autoantibodies to types III and V collagen were noted in 87.5% (28/32) and 90.6% (29/32) of EB sera, respectively, while being only rarely noted in sera from other patient groups. Similarly, autoantibodies to type IV collagen and laminin were detected in 50% (16/32) and 40.6% (13/32) of EB sera, especially from patients with simplex and dystrophic forms of the disease. These data suggest that selected interstitial and basement membrane-associated collagens and laminin may become autoimmunogenic in all three forms of inherited EB in contrast to their relative lack of immunogenicity in at least some of the other intraepidermal and subepidermal blistering disorders. The role, if any, of these autoantibodies in the induction or perpetuation of blistering in EB awaits further studies.

Growth stimulation of FRTL-5 and of human thyroid epithelial cells with immunoglobulins from patients with non-autoimmune thyroid diseases

Journal Article Growth stimulation of FRTL-5 and of human thyroid epithelial cells with immunoglobulins from patients with non-autoimmune thyroid diseases Get access M Oethinger, M Oethinger Klinik für Innere Medizin, Medizinische Universität Lübeck Search for other works by this author on: Oxford Academic Google Scholar B E Wenzel, B E Wenzel Klinik für Innere Medizin, Medizinische Universität Lübeck Search for other works by this author on: Oxford Academic Google Scholar S Grammerstorf, S Grammerstorf Klinik für Innere Medizin, Medizinische Universität Lübeck Search for other works by this author on: Oxford Academic Google Scholar R Gutekunst, R Gutekunst Klinik für Innere Medizin, Medizinische Universität Lübeck Search for other works by this author on: Oxford Academic Google Scholar P C Scriba P C Scriba Klinik für Innere Medizin, Medizinische Universität Lübeck Search for other works by this author on: Oxford Academic Google Scholar Acta Endocrinologica (Norway), Volume 117, Issue 4_Supplement, Apr 1988, Pages S45–S46, https://doi.org/10.1530/acta.0.117S045 Published: 01 April 1988

Lupus anticoagulant: a clinical and laboratory study of 100 cases.

The clinical and laboratory features of 100 patients with lupus anticoagulant (LA) are reviewed. Subjects were divided into three groups according to their age (1-5, 15-35, 45-89 years). Female prevalence was observed in each group and overall F/M ratio was 3/1. An underlying autoimmune disease (principally lupus erythematosus) was found in 47 cases (10% of the children, 80% of the 15-35-year-old patients and 37% of the elderly patients). Biological criteria for the LA diagnosis were prolonged activated partial thromboplastin time and diluted thromboplastin time (1.3 x control), not corrected after addition of control to patient's plasma. Thromboplastin time was normal in 77 patients. Other types of coagulation inhibitors were eliminated by specific factor assays (with a 10-fold increase of cephalin concentration when necessary). Twenty-three thrombotic episodes were observed. No significant difference was found in the incidence of thrombosis between the autoimmune and non-autoimmune disease group, but the age when first thrombosis occurred was clearly lower in the former. Fourteen obstetrical accidents were noted in eight women but 13 pregnancies terminated without accident. Four patients experienced haemorrhagic complications; they all presented with a severe thrombocytopenia associated with the LA. In our experience, LA is a frequent coagulation abnormality, associated in about half of the cases with a clearly defined autoimmune disease. Clinical presentation appears as notably different according to the patient's age; it is particularly noteworthy that in nine out of 10 children, LA disappeared spontaneously within 6 months.

Occurrence of thyrocyte HLA class II expression in a wide variety of thyroid diseases: relationship with lymphocytic infiltration and thyroid autoantibodies.

The proteins of the major histocompatibility system (HLA in humans) play an essential role in the regulation of immune responses due to their involvement in the presentation of antigen to T lymphocytes. Thyroid follicular cells (thyrocytes) from patients with Graves' disease and Hashimoto's thyroiditis demonstrate increased expression of HLA class I and aberrantly or inappropriately express class II antigens, a phenomenon that may play an important role in the pathogenesis of these autoimmune diseases. To establish if these changes in the expression of HLA molecules are characteristic of thyroid autoimmune disease, the immunopathological features (including class I and class II antigen expression) of 100 thyroidectomy specimens from patients with nonautoimmune thyroid disease were studied by indirect immunofluorescence, and the results compared with the findings in specimens from 14 patients with Graves' disease and 12 subjects undergoing laryngectomies for carcinoma. Increased class I product expression was found in 61% of all tissues studied, with maximal occurrence in papillary carcinomas (100%) and Graves' disease (86%), but it was also detected in 50% of the glands containing nodular lesions and in 16% of the control glands. Inappropriate class II molecule expression was found in Graves' disease (71%), hyperplastic nodules (53%), multinodular glands (44%), papillary carcinomas (38%), and 16% of the control glands. In summary, an increase in inappropriate HLA class I and class II expression was very common in nonautoimmune thyroid glands, but it generally occurred in the context of lymphocytic infiltration and thyroid autoantibodies (i.e. focal thyroiditis). Multiple correlation analyses of these 4 phenomena indicated heterogeneity in the mechanism leading to the inappropriate expression of thyrocyte class II antigens in the different conditions studied.

Thyroid autoantibodies: a good marker for the study of symptomless autoimmune thyroiditis.

In 3737 subjects without clinically thyroid disorders we evaluated the incidence of thyroid microsomal and thyroglobulin antibodies. These autoantibodies were found in 7% of a normal population, in 9% of patients with various non-autoimmune diseases, and in 11-16% of groups who either had or were at risk for autoimmune diseases: patients with IDDM, vitiligo, alopecia areata, idiopathic hypoparathyroidism, Addison's disease, and first-degree relatives of IDDM patients. Functional thyroid evaluation with TRH test was performed in 197 seropositive subjects and 144 seronegative controls. One-quarter (26%) of the subjects with thyroid autoantibodies showed functional abnormalities on TRH testing, whereas only 2.8% of the 144 seronegative controls showed subclinical hypothyroidism. After an observation period of 12-44 months, 102 persistently seropositive subjects were reassessed and 31% of them showed an impairment in TRH test response.

Age‐dependent isotype variation during secondary immune response in MRL/lpr mice producing autoanti‐γ‐globulin antibodies

A profound inability to produce IgG anti-2,4,6-trinitrophenyl (TNP) antibodies during the secondary immune response elicited by a T-dependent antigen was observed in aged MLR/lpr mice. This unresponsiveness is associated with a significantly low indirect anti-TNP plaque-forming cell response and a weak in vitro anti-TNP response upon the culture of keyhole limpet hemocyanin-primed T cells and TNP-primed B cells in the presence of TNP. The markedly low IgG anti-TNP response observed in aged MLR/lpr mice cannot be related to the presence of rheumatoid factors which are observed during the secondary response, since MRL +/+ and 129/J mice, (non-autoimmune disease strains), also produce significant amounts of anti-gamma-globulin antibodies yet mount a strong IgG anti-TNP response.

Autoimmune thyroid disease: purification and phenotypic analysis of intrathyroid T cells.

A phenotypic analysis of T cells infiltrating the thyroid of patients with autoimmune thyroid disease (both Graves' disease and Hashimoto's thyroiditis) was performed. T lymphocytes were purified from mononuclear cells extracted from surgically removed tissue. The following markers were evaluated: la antigens, MLR4 antigen (expressed on activated T cells) 5/9 antigen (expressed on a subset of lymphocytes containing the whole "helper-inducer" activity in vitro), Fc gamma-receptors, B9 antigen (expressed by cytotoxic, or precursor of cytotoxic, T cells). We observed increased percentages of 5/9-, MLR4- and la-positive T cells with respect to peripheral blood in both HT and GD: on the contrary, in specimens from nonautoimmune thyroid diseases mononuclear infiltrate was minimal, and even T cell evaluation was not possible. In addition, B9- and Fc gamma-positive T cells were increased in Hashimoto's, but not in Graves' thyroid tissue, thus suggesting a different role of cytotoxic effector mechanisms in the two diseases.

Isolation and characterization of mononuclear cells from various thyroid tissue specimens

Extensive studies of humoral and cell mediated autoimmune responses to thyroid antigens have been performed in order to understand the underlying mechanisms of autoimmune thyroid disorders. Very little is known, however, about the nature of the lymphocyte subpopulations in the thyroid gland and their possible involvement in the pathogenesis of thyroid diseases. We have developed a Percoll gradient technique to separate mononuclear cells from thyroid cells of resected thyroid glands. Thyroid tissue was minced, incubated with Dispase and passed through a tissue sieve. The filtrate was layered onto a four step discontinuous Percoll gradient (densities 1.140, 1.077, 1.061, 1.030 g/ml). Thyroid cells appeared in band II and mononuclear cells in band III. Mononuclear cells were characterized using the monoclonal antibodies OKT-3, OKT-8, OKI-a and OKM-1, and the levels of these populations in peripheral blood and thyroid tissue compared. Patients have been classified by conventional clinical, immunological and histological criteria. The studies involved thyroid tissues from 8 patients with euthyroid nodular goitre, 7 patients with Graves' disease and 1 with Hashimoto's thyroiditis. In the thyroid tissue of non-autoimmune thyroid diseases we find significantly less OKT-3+ cells compared to peripheral blood. In thyroid tissue of autoimmune thyroid diseases there are significantly less OKT-8+ cells compared to peripheral blood. These preliminary results might be linked to the hypothesis of decreased suppressor T-cell activity in autoimmune thyroid disease.

DEFECTIVE REPAIR OF 0 6-METHYLGUANINE IN AUTOIMMUNE DISEASES

On the premise that somatic mutations may be involved in the pathogenesis of diseases such as systemic lupus erythematosus and rheumatoid arthritis, the proficiency of repair of 0 6-methylguanine, a powerful, premutagenic, directly miscoding base lesion, was examined in the DNA of peripheral-blood mononuclear cells (mainly lymphocytes) from patients with such diseases. The capacity of lymphocytes to repair this lesion was impaired in many patients with autoimmune disease. In some healthy controls repair was also defective, whereas in other, non-autoimmune diseases, it was not. These findings support the hypothesis that this defect of repair was not simply a result of the disease state. It is therefore postulated that defective repair of 0 6-methylguanine could be one of the factors determining the susceptibility to autoimmune diseases in genetically predisposed individuals.

Myasthenia gravis in infancy

Symptoms of myasthenia gravis in infancy may occur from passive transfer of maternal disease, acquired autoimmune disease, or nonautoimmune hereditary disease. Of nine patients with infantile-onset myasthenia who were not born to mothers with the disease, two had detectable antibody to acetylcholine receptor. Patients with or without antibodies were clinically indistinguishable, except for the occurrence of similar disease in siblings of patients without antibody. Differentiation of autoimmune and hereditary myasthenia in infancy is necessary for appropriate therapeutic measures and genetic counseling. Antibody determinations provide a useful aid in this differentiation.

Myasthenia gravis in infancy.

Symptoms of myasthenia gravis in infancy may occur from passive transfer of maternal disease, acquired autoimmune disease, or nonautoimmune hereditary disease. Of nine patients with infantile-onset myasthenia who were not born to mothers with the disease, two had detectable antibody to acetylcholine receptor. Patients with or without antibodies were clinically indistinguishable, except for the occurrence of similar disease in siblings of patients without antibody. Differentiation of autoimmune and hereditary, myasthenia in infancy is necessary for appropriate therapeutic measures and genetic counseling. Antibody determinations provide a useful aid in this differentiation.

Tubuloreticular structures and antinuclear antibodies in autoimmune and non-autoimmune diseases.

Tissues obtained at random from patients suffering from autoimmune and non-autoimmune diseases were studied for the presence of tubuloreticular structures (TRS). It could be demonstrated that the occurrence of TRS in renal tissue is not a specific characteristic of systemic lupus erythematosus whereas the presence of such structures in skin tissue might be suggestive for this disease. The serum of some of the patients could be studied for the presence of antinuclear antibodies (ANA). A statistically significant correlation was found between TRS and ANA in the group of patients with autoimmune diseases. The possibility is discussed that this correlation might favour the theory that viruses may be involved in the aetiology of autoimmune diseases, particularly of systemic lupus erythematosus.