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M A Agius

Publications and source records attributed to M A Agius.

At least 19 recordsLinked to original sources
PubMed1997

Role of antiribosomal P protein antibodies in the diagnosis of lupus isolated to the central nervous system.

BACKGROUND: When lupus presents with isolated central nervous system findings, the usual serologic markers are often absent and diagnostic difficulty with a delay in treatment is common. OBJECTIVE: To report the usefulness of antiribosomal P protein antibodies in the diagnosis of lupus isolated to the central nervous system when results of tests for anti-double-stranded DNA antibodies are negative. DESIGN: Case report. SETTING: University medical center. PATIENT: The patient was evaluated and treated on referral and follow up for 1 year. RESULTS: We describe a patient with acute onset of psychosis followed by coma and focal clonic movements with undetectable DNA antibodies. Serum antiribosomal P protein antibody levels were elevated. Steroid therapy was followed by marked clinical improvement and a decrease in antibody titer. CONCLUSION: Antiribosomal P protein antibodies provide an important confirmatory test for the diagnosis of lupus isolated to the central nervous system when results of tests for anti-double-stranded DNA antibodies are negative.

Adult↗
PubMed1994

Myasthenia gravis: pathogenesis and treatment.

Much is known about the pathogenesis of MG. This information has provided a rational basis for treatment of the disease, which is very effective. On the other hand, present treatments are limited by significant adverse effects. Our knowledge of pathogenesis also provides clues for the development of new, effective, but less toxic treatments. In addition, knowledge of the autoimmune mechanisms in MG may be useful in devising better treatments for the many human autoimmune diseases that are less well understood.

Animals↗
PubMed1994

Acquired myasthenia gravis. Immunopathology.

Much of the remarkable advance in our understanding of the immunopathology of MG relates to the availability of two gifts of nature that permit the ready purification of the antigen, AChR. Immunization of experimental animals with AChR has led to the development of the extremely faithful animal model, EAMG. Analysis of both EAMG and MG has revealed that the effector agents in this autoimmune disease are anti-AChR antibodies, whose production is regulated by anti-AChR CD4+ T cells. The pathogenic effects on neuromuscular transmission are mediated by antibody-induced antigenic modulation of end-plate AChR, end-plate membrane destruction through complement fixation and recruitment of inflammatory cells, and antibody-induced blockade of the function of the remaining AChR molecules. The origin of MG remains unknown. One theory proposes that dysregulation of the thymic control of tolerance plays an important role. An alternative hypothesis is that tolerance is broken as the result of a vigorous immune response directed against an invading microorganism that expresses a molecule that is similar to AChR, so-called molecular mimicry. This "normal" response eventually cross-reacts with self-AChR, resulting in the autoimmune damage. Our current knowledge of MG has suggested a number of possible sites of therapeutic intervention that are under active study. Future information concerning the origin of the disease will likely be useful in the design of more effective treatment for this and other related autoimmune diseases.

Animals↗
PubMed1988

Monoclonal anti-idiotopic antibodies against myasthenia-inducing anti-acetylcholine receptor monoclonal antibodies. Preponderance of nonparatope-directed antibodies affecting antigen binding.

To analyze components of the idiotypic network in experimental autoimmune disease, we produced 17 isogeneic anti-idiotopic monoclonal antibodies (anti-Id) against two experimental autoimmune myasthenia gravis-producing anti-acetylcholine receptor (anti-AChR) monoclonal antibodies. We studied the binding of five of the anti-Id to the anti-AChR monoclonal antibodies bearing the complementary idiotopes (Id-mAb). They bound with Kd values ranging from 0.06 to 0.86 nM, values comparable to those of Id-mAb:AChR complexes (0.26 and 0.34 nM). All of the anti-Id tested moderately inhibited the binding of AChR to Id-mAb, whereas for each anti-Id, AChR either strongly inhibited anti-Id binding or had no effect on anti-Id binding. Hence, the inhibition of Id-mAb:AChR binding by anti-Id was not reciprocal with the inhibition of anti-Id:Id-mAb binding by AChR. For each anti-Id, the relative affinities of anti-Id and AChR for Id-mAb together with the lack of symmetry of inhibition by anti-Id compared to inhibition by AChR indicate that these two "ligands" are not competitive inhibitors. Consequently, anti-Id and AChR do not bind to overlapping sites on the Id-mAb, suggesting that the observed inhibition is mediated allosterically. This may be a common mechanism of anti-Id:Id binding, which would have important implications for the mechanism of anti-Id-induced suppression.

Allosteric Regulation↗