Disease relevance of Stiff-Person Syndrome

• We have previously reported the presence of autoantibodies against glutamic acid decarboxylase (GAD) in a patient with stiff-man syndrome, epilepsy, and insulin-dependent diabetes mellitus [1].
• Autoantibodies to glutamic acid decarboxylase in a patient with stiff-man syndrome, epilepsy, and type I diabetes mellitus [2].
• Rhabdomyolysis and paraneoplastic stiff-man syndrome with amphiphysin autoimmunity [3].
• The single or double amino-acid mutants can be used to distinguish some anti-glutamic acid decarboxylase-65 autoantibodies and could prove useful in distinguishing Type I diabetic from autoimmune polyendocrine syndrome and stiff-man syndrome patients' sera as well as to study changes in antibody patterns during disease progression [4].
• No reactivity against this latter antigen was found in sera of patients with Type 1 (insulin-dependent) diabetes mellitus (n = 9), Graves' disease (n = 5), autoimmune gastritis (n = 4), idiopathic Addison's disease (n = 7), or stiff-man syndrome (n = 2) [5].

High impact information on Stiff-Person Syndrome

• CONCLUSIONS: Intravenous immune globulin is a well-tolerated and effective, albeit costly, therapy for patients with stiff-person syndrome and anti-GAD65 antibodies [6].
• These findings support the idea that an impairment of neuronal pathways that operate through gamma-aminobutyric acid is involved in the pathogenesis of stiff-man syndrome, and they raise the possibility of an autoimmune pathogenesis [2].
• We investigated the possible existence of autoimmunity against the nervous system in a patient with stiff-man syndrome associated with epilepsy and Type I diabetes mellitus [2].
• Resolution of stiff-man syndrome with cortisol replacement in a patient with deficiencies of ACTH, growth hormone, and prolactin [7].
• Glutamic acid decarboxylase is attracting much interest because of its putative involvement in two clinical disorders: stiffman syndrome and insulin-dependent diabetes [8].

Chemical compound and disease context of Stiff-Person Syndrome

• Stiff-man syndrome and clonazepam [9].
• Higher autoantibody levels and recognition of a linear NH2-terminal epitope in the autoantigen GAD65, distinguish stiff-man syndrome from insulin-dependent diabetes mellitus [10].
• Improvement of stiff-man syndrome with vigabatrin [11].
• Baclofen in the treatment of stiff-man syndrome [12].
• This suggests the involvement in the stiff-man syndrome of a central norepinephrine neuronal system that has net excitatory effects upon motoneurons, a system whose activity can be increased slightly by levodopa and decreased markedly by diazepam, with corresponding changes in stiffness [13].

Biological context of Stiff-Person Syndrome

• Amphiphysin (amphiphysin I), a dominant autoantigen in paraneoplastic Stiff-man syndrome, is a neuronal protein highly concentrated in nerve terminals, where it has a putative role in endocytosis [14].
• Primary structure of human amphiphysin, the dominant autoantigen of paraneoplastic stiff-man syndrome, and mapping of its gene (AMPH) to chromosome 7p13-p14 [15].

Anatomical context of Stiff-Person Syndrome

• We screened synthetic peptide libraries dedicated to bind to HLA-DR3, which predisposes to both diseases, using clonal CD4(+) T cells reactive to GAD65 isolated from a prediabetic stiff-man syndrome patient [16].
• Cytoplasmic islet cell antibodies recognize distinct islet antigens in IDDM but not in stiff man syndrome [17].
• In addition, sequence comparisons revealed that amphiphysin, a protein first found in synaptic vesicles of chicken and shown to be the autoantigen of Stiff Man syndrome, presents similarity with both Rvs proteins [18].
• The diagnosis of stiff-man syndrome was made based on not only clinical findings and the characteristic electromyographic pattern but also the presence of antibodies to glutamic acid decarboxylase in the serum and cerebrospinal fluid [19].

Gene context of Stiff-Person Syndrome

• GAD65 is targeted by different patterns of autoantibodies [glutamic acid decarboxylase (GAD)-AAbs] in insulin-dependent diabetes mellitus (IDDM) and stiff-man syndrome (SMS) [20].
• Autoimmunity to gephyrin in Stiff-Man syndrome [21].
• Autoantibodies to 65 kDa glutamic acid decarboxylase (GAD65) are produced in many patients with autoimmune polyendocrine syndrome type II (APS-II) or stiff-man syndrome (SMS) and are heterogeneous in their epitope specificities, recognizing both conformational and linear determinants [22].
• Analysis of GAD65 autoantibodies in Stiff-Person syndrome patients [23].
• GAD-65 is a dominant autoantigen in stiff-man syndrome and insulin-dependent diabetes mellitus [24].

Analytical, diagnostic and therapeutic context of Stiff-Person Syndrome

• The 16 lyophilized coded samples consisted of sera from healthy control subjects (n = 2), IDDM patients (n = 3), a patient with polyendocrine autoimmunity (n = 1), and duplicate dilutions of plasmapheresis serum from a patient with stiff-man syndrome (SMS) [25].
• Atypical stiff-person syndrome with spinal MRI findings, amphiphysin autoantibodies, and immunosuppression [26].
• Vaccination against herpes zoster, small RNA against ALS and IgG antibodies in stiff-person syndrome [27].
• Radioimmunoassay for glutamic acid decarboxylase (GAD65) autoantibodies as a diagnostic aid for stiff-man syndrome and a correlate of susceptibility to type 1 diabetes mellitus [28].
• Her clinical features and electromyography suggested Stiffman syndrome, and her response to high-dose diazepam and baclofen confirmed the diagnosis [29].

References