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At least 163 records · Page 9Linked to original sources
PubMed1990

The humoral autoimmune response to vasectomy described by immunoblotting from two-dimensional gels and demonstration of a human spermatozoal antigen immunochemically crossreactive with the D2 adhesion molecule.

The specificity of human serum antispermatozoal antibodies was analysed by immunoblotting after two-dimensional electrophoretic separation (IEF/PAGE) of human spermatozoal proteins. Spermatozoal proteins with Mr 20-200 kDa and pI between 4.5 and 7.8 were analysed for antigenicity. Fifteen sera (four female and 11 male) were analysed for antisperm IgG antibodies. Individual IgG binding patterns were observed. The antisperm antibody response to ligation of the vas deferens was described by immunoblotting analysis of sera taken pre- and post-operatively at regular intervals from three men undergoing vasectomy. The high resolution of spermatozoal antigens allowed a specific description of the humoral response to vasectomy. Both appearance and disappearance of spots were observed in the postoperative period, indicating induction of new antibody producing clones and binding of former free antibodies in circulating immunocomplexes. In one patient five glycosylated proteins induced an IgM response 2 weeks after vasectomy. Four of these autoantigens with Mr of 122 kDa, 119 kDa, 104 kDa and 77 kDa and pI of 5.9, 6.1, 7.7 and 6.0, respectively, have previously been shown to be intrinsic membrane proteins (Naaby-Hansen, (1990) J., Reprod. Immunol. 17). An observed immunochemical crossreactivity between the interneuronal adhesion molecule, D2-protein and an antigen extracted from human sperm and teratomas is discussed.

Adolescent↗
PubMed2006

New insights to the immunopathology and autoimmune responses in primary biliary cirrhosis.

Primary biliary cirrhosis (PBC) is an autoimmune liver disease with profound changes in different compartments of the immune system, including those involved in innate, and adaptive immunity. New data from epidemiological studies of PBC have reinforced the thesis that the cause for this relatively uncommon disease is likely to be a combination of both environmental factors and a susceptible genetic predisposition. Recent findings of abnormalities of the innate immune system in PBC suggest that they may serve as links between the environmental factors and the early events in PBC development. Viral and bacterial infections as well as xenobiotics are some of the potential environmental factors that have been implicated in this complex process. Identification of the etiological factors for PBC will point to new preventive or therapeutic treatments.

Adaptation, Biological↗
PubMed1976

The autoimmune response to male reproductive tissues of rabbits. IV. Induction of autosensitization to central accessory tissue by the intraabdominal release of endogenous secretions.

A study is described in which tissue- and secretion-specific autosensitization was induced in adult male rabbits through intraabdominal cannulation of one or more of their central accessory glands. Both primary and secondary humoral antibodies were elicited by this procedure, as determined by tanned cell hemagglutination and passive hemolysis, i.e., complement fixation. The secondary antibody responses were elicited by (i) cannulation of animals which had been previously stimulated by cryosurgery or combined cryosurgery and injection of pooled accessory tissue extract, and (ii) isoinjection of previously cannulated animals with accessory tissue extract. Primary antibody responses were less in animals castrated at the time of cannulation compared to those in noncastrated animals; but, paradoxically, subsequent challenges with tissue extract induced higher secondary antibody titers in castrated animals. These observations may be explained in castrates by (i) reduced uptake of antibodies--a result of the sparing effect on circulating antibodies in castrated animals because of accessory tissue atrophy, or (ii) increased production of antibodies through postcastration immune enhancement. In noncastrates secondary antibody depression may be related to (i) increased absorption of antibodies by an accessory gland complex which is much larger than that found in castrates, or (ii) tolerance, due to exposure of the antibody-producing system to excess accessory tissue antigen.

Abdomen↗
PubMed1997

A peptide composed of tandem analogs of two myasthenogenic T cell epitopes interferes with specific autoimmune responses.

Myasthenia gravis (MG) is a T cell-regulated, antibody-mediated autoimmune disease. Two peptides representing sequences of the human acetylcholine receptor alpha-subunit, p195-212 and p259-271, were previously shown to stimulate peripheral blood lymphocytes of patients with MG and were found to be immunodominant T cell epitopes in SJL and BALB/c mice, respectively. Single amino acid substituted analogs of p195-212 (analog Ala-207) and p259-271 (analog Lys-262) were synthesized. We showed that analogs Ala-207 and Lys-262 inhibited, in vitro and in vivo, the proliferative responses of T cell lines specific to the relevant peptide and lymph node cells of mice immunized to p195-212 and p259-271, respectively. To inhibit T cell responses to both peptides (p195-212 and p259-271), we synthesized dual analogs composed of the tandemly arranged two single (Ala-207 and Lys-262) analogs (dual analog) either sequentially (Ala-207-Lys-262) or reciprocally (Lys-262-Ala-207). In the present study, we report that both dual analogs could bind to major histocompatibility complex class II molecules on antigen-presenting cells of SJL and BALB/c mice. Analog Lys-262-Ala-207, which bound more efficiently to major histocompatibility complex class II molecules, was found to inhibit the proliferative responses of both p195-212- and p259-271-specific T cell lines. Furthermore, the analog inhibited the in vivo priming of lymph node cells of both SJL and BALB/c mice when administered i.v., i.p., or per os. The dual analog Lys-262-Ala-207 could also immunomodulate myasthenogenic manifestations in mice with experimental autoimmune MG induced by inoculation of a pathogenic T cell line. Thus, a single peptide that is composed of analogs to two epitope specificities can be used to regulate T cell responses and disease associated with each epitope.

Amino Acid Sequence↗
PubMed1998

Autoimmune responses to the beta cell autoantigen, insulin, and the INS VNTR-IDDM2 locus.

Type 1 diabetes is associated with autoimmunity to insulin. Genetic susceptibility to type 1 diabetes is polygenic and includes the INS VNTR-IDDM2 locus which may regulate the expression of insulin in pancreas and thymus. In order to determine whether insulin autoimmunity could be attributed to a genetic susceptibility conferred by the INS VNTR-IDDM2 locus, peripheral blood T cell proliferation to human insulin and insulin autoantibodies (IAA) was measured in patients with new onset type 1 diabetes and control subjects. IAA were detected in 21 of 53 patients and in none of 25 control subjects, while T cell responses were low (stimulation index range 0.4-7.2) and similar in both groups. Both antibody and T cell responses were higher in younger subjects and IAA were more prevalent in patients with the HLA-DR4 allele. No relationship was observed between humoral and cellular responses to insulin. No association was found between the INS VNTR-IDDM2-susceptible allele and insulin autoimmunity. Increased T cell responses and IAA were found in patients with either the diabetes-susceptible or the diabetes-protective INS VNTR-IDDM2 locus genotypes, and increased T cell responses were also found in control subjects with either susceptible or protective INS VNTR-IDDM2 locus genotypes. This study confirms that primary T cell proliferative responses to insulin are low and detectable also in control subjects. The detection of T cell proliferation and autoantibodies to insulin in subjects with and without the protective INS VNTR-IDDM2 locus genotypes does not support the hypothesis of an allele-specific capacity for tolerance induction which could determine a susceptibility to develop autoimmunity against the insulin protein and subsequently diabetes.

Adolescent↗
PubMed1993

Myasthenia gravis: an autoimmune response against the acetylcholine receptor.

Myasthenia gravis (MG) is an organ-specific autoimmune disease caused by an antibody-mediated assault on the muscle nicotinic acetylcholine receptor (AChR) at the neuromuscular junction. Binding of antibodies to the AChR leads to loss of functional AChRs and impairs the neuromuscular signal transmission, resulting in muscular weakness. Although a great deal of information on the immunopathological mechanisms involved in AChR destruction exists due to well-characterized animal models, it is not known which etiological factors determine the susceptibility for the disease. This review gives an overview of the literature on the AChR, MG and experimental models for this autoimmune disease.

Adult↗
PubMed1998

C1q as antigen in humoral autoimmune responses.

The observation of anti-C1q antibodies (C1qAb) in patients with various autoimmune diseases has led to the establishment of a strong correlation between these antibodies and renal involvement in patients with systemic lupus erythematosus (SLE). The measurement of anti C1q antibodies requires detailed insight in the reactivity of C1q with immune complexes and the methods to detect C1q as an antigen by solid phase assays. In this overview we describe the pitfulls of the anti C1qAb assay and its use in the measurement of C1qAb. Further we discuss the relevance of C1qAb in the pathogenesis of SLE and especially in relation to lupus nephritis.

Adult↗
PubMed1996

Immunologic markers for differentiation of autoimmune responses.

Several approaches have been directed at identifying accurate parameters for the measurement of disease activity in autoimmune disorders, both in humans and in experimental animal models. A great deal of previous effort has focused on determining what constitutes antigenic epitopes on various autologous proteins or tissue components, which then can generate an immune response in the host. Much of this work has been clouded by the fact that normal subjects (both animal and human) seem to mount an immune response to myriad autologous proteins, characterized by the formation of antibodies known as natural autoantibodies. During the course of certain autoimmune diseases such as systemic lupus erythematosus (SLE) or Wegener's granulomatosis (WG), patients produce what appear to be autoantibodies reacting with autologous components such as DNA and Sm antigen (SLE) or proteinase-3 (WG). Low levels of these same autoantibodies are present in IgG derived from normal subjects. Recently, we have found that IgG anti-F(ab')2 from normal subjects, affinity-purified from immunoabsorbent columns of human F(ab_)2 Sepharose, exhibits not only anti-F(ab')2 but also anti-dsDNA and anti-Sm activity. These antibodies constitute an average of 0.02% of normal serum IgG. Similar findings have also been observed in SLE patients with active disease. Our findings suggest that perturbation of the idiotypic network may represent an important fundamental aspect of many autoimmune disorders.

Animals↗
PubMed1999

Fine specificity of the autoimmune response to the Ro/SSA and La/SSB ribonucleoproteins.

The fine specificity of the Ro and La proteins has been studied by several techniques. In general, there is agreement in a qualitative sense that autoantibodies bind multiple epitopes. For some specific antibody binding, different studies agree quantitatively, for instance, the binding of the carboxyl terminus of 60-kd Ro as described by 2 studies using different techniques and the presence of an epitope within the leucine zipper of 52-kd Ro. In addition, there is general agreement about the location of a prominent epitope at the RRM motif region of the La molecule. On the other hand, the many specific epitope regions of the molecules differ among these studies. These discrepancies are likely the result of using different techniques, sera, and peptide constructs as well as a result of inherent advantages and disadvantages in the individual approaches. Several theories concerning the origin of not only the antibodies, but also the diseases themselves, have been generated from studies of the fine specificity of antibody binding. These include a theory of a primordial foreign antigen for anti-Ro autoimmunity, molecular mimicry with regard to La and CCHB, as well as the association of anti-Ro with HLA. These remain unproven, but are of continuing interest. An explanation for the association of anti-60-kd Ro and anti-52-kd Ro in the sera of patients has sprung from evaluating antibody binding. Data demonstrating multiple epitopes are part of a large body of evidence that strongly suggests an antigen-driven immune response. This means that the autoantigens are directly implicated in initiating and sustaining autoimmunity in their associated diseases. A number of studies have investigated the possibility of differences in the immune response to these antigens in SS and SLE sera. While several differences have been reported, none have been reproduced in a second cohort of patients. Furthermore, none of the reported differences may be sufficiently robust for clinical purposes, such as distinguishing between SS with systemic features and mild SLE, although some might be promising. For instance, in at least 3 groups of SLE patients, no binding of residues spanning amino acids 21-41 of 60-kd Ro has been found. Meanwhile, 1 of those studies found that 41% of sera from patients with primary SS bound the 60-kd Ro peptide 21-41. Perhaps future studies will elaborate a clinical role of such a difference among SS and SLE patients. Study of the epitopes of these autoantigens has, in part, led to a new animal model of anti-Ro and anti-La. Non-autoimmune-prone animals are immunized with proteins or peptides that make up the Ro/La RNP. Such animals develop an autoimmune response to the entire particle, not just the immunogen. This response has been hypothesized to arise from autoreactive B cells. In another, older animal model of disease, the MRL-lpr/lpr mouse, B cells have recently been shown to be required for the generation of abnormal, autoreactive T cells. Thus, there are now powerful data indicating that B cells that produce autoantibodies are directly involved in the pathogenesis of disease above and beyond the formation of immune complexes. Given that the autoreactive B cell is potentially critical to the underlying pathogenesis of disease, then studying these cells will be crucial to further understanding the origin of diseases associated with Ro and La autoimmunity. Hopefully, an increased understanding will eventually lead to improved treatment of patients. Progress in the area of treatment will almost surely be incremental, and studies of the fine specificity of autoantibody binding will be a part of the body of basic knowledge contributing to ultimate advancement. In the future, the animal models will need to be examined with regard to immunology and immunochemistry as well as genetics. The development of these autoantibodies has not been studied extensively because upon presentation to medical care, virtually all patients have a full-

Animals↗
PubMed1991

Autoimmune response induction and regulation in rat erythrocyte-immunized mice.

The process of antibody formation to self-red blood cells (RBC) has been studied in rat RBC (rRBC)-immunized mice. A positive correlation was noted between antibody production to mouse RBC (mRBC) and rRBC in some mouse strains. The low responsiveness on both indices was overcome by s.c. injections of rRBC in low doses. rRBC-tolerant mice exhibited lower levels of antibody production to mRBC. Splenocytes from rRBC-immunized donors, when transferred to irradiated recipients, revealed enhanced and accelerated anti-mRBC and anti-rRBC antibody production in response to rRBC but not to autologous mRBC. Consequently, the autoimmune process is not accompanied by disordered immunologic tolerance to self-RBC and requires participation of Th responding to foreign epitopes of rRBC antigens. Splenocytes from rRBC-immunized donors, when transferred to non-irradiated recipients, inhibited antibody production to mRBC. The suppressive effect was not abrogated by pretreating donors or recipients with low doses of cyclophosphamide (CP) or by pretreating donors with antibodies to I-J. It was abrogated by the elimination of cells of donor origin within 8-9 days after transfer. Inoculation of antibodies to rRBC in immunized mice on a schedule imitating their splenocyte transfer dynamics inhibited antibody production to mRBC. Therefore, it can be assumed that the suppressive effect of cell transfer is accounted for, not by suppressors or their inducers, but by antibodies to rRBC on the basis of feedback regulation.

Anemia, Hemolytic, Autoimmune↗
PubMed2001

Neuronal survival after CNS insult is determined by a genetically encoded autoimmune response.

Injury to the CNS is often followed by a spread of damage (secondary degeneration), resulting in neuronal losses that are substantially greater than might have been predicted from the severity of the primary insult. Studies in our laboratory have shown that injured CNS neurons can benefit from active or passive immunization with CNS myelin-associated antigens. The fact that autoimmune T-cells can be both beneficial and destructive, taken together with the established phenomenon of genetic predisposition to autoimmune diseases, raises the question: will genetic predisposition to autoimmune diseases affect the outcome of traumatic insult to the CNS? Here we show that the survival rate of retinal ganglion cells in adult mice or rats after crush injury of the optic nerve or intravitreal injection of a toxic dosage of glutamate is up to twofold higher in strains that are resistant to the CNS autoimmune disease experimental autoimmune encephalomyelitis (EAE) than in susceptible strains. The difference was found to be attributed, at least in part, to a beneficial T-cell response that was spontaneously evoked after CNS insult in the resistant but not in the susceptible strains. In animals of EAE-resistant but not of EAE-susceptible strains devoid of mature T-cells (as a result of having undergone thymectomy at birth), the numbers of surviving neurons after optic nerve injury were significantly lower (by 60%) than in the corresponding normal animals. Moreover, the rate of retinal ganglion cell survival was higher when the optic nerve injury was preceded by an unrelated CNS (spinal cord) injury in the resistant strains but not in the susceptible strains. It thus seems that, in normal animals of EAE-resistant strains (but not of susceptible strains), the injury evokes an endogenous protective response that is T-cell dependent. These findings imply that a protective T-cell-dependent response and resistance to autoimmune disease are regulated by a common mechanism. The results of this study compel us to modify our understanding of autoimmunity and autoimmune diseases, as well as the role of autoimmunity in non-autoimmune CNS disorders. They also obviously have far-reaching clinical implications in terms of prognosis and individual therapy.

Animals↗