Five individuals without GAD65 and GlyR antibodies had autoantibodies against additional known antigens (2 amphiphysin, 2 GABAaR, and 1 DPPX;eMaterial in Product). == Clinical End result == Clinical outcome was available for 75 patients (62.0%), having a median follow-up of 18 months (IQR, 1160 weeks). clinical features of SPSD. Data analysis was performed from July 1,2015. through November 1,2015. == MAIN OUTCOMES AND Steps == Analysis of clinical-immunologic associations, including autoantibodies to 8 proteins indicated in inhibitory synapses. == RESULTS == The median age of the individuals was 51 years (interquartile range, 4061 years), and 75 (62.0%) were woman. Fifty (41.3%) had SPS, 37 (30.6%) had SPS-plus. 24 (19.8%) had SLS, and 10 (8.3%) had SPS or SLS overlapping with ataxia, epilepsy, or encephalitis. Fifty-two individuals (43.0%) had glutamic acid decarboxylase (GAD65) antibodies (2 with -aminobutyric acid-A [GABA-A] receptor antibodies), 24 (19.8%) had 1,-subunit of the glycine receptor (GlyR) antibodies (2 with Ambrisentan (BSF 208075) GAD65 antibodies), 5 (4.1%) had additional antibodies, and 40 (33.1%) tested negative for antibodies. None experienced gephyrin or glycine transporter antibodies. Among the main immunologic organizations (GAD65 antibodies, GlyR antibodies, and antibody bad), those with GAD65 antibodies were more likely to be woman (45 [86.5%] Ambrisentan (BSF 208075) of 52,8 [36.4%] of 22, and 18 [45.0%] of 40, respectively;P <.001), have systemic autoimmunity (34 [65.4%] of 52.7 [31.8%] of 22. and 13 [32.5%] of 40. respectively;P= .004), and have longer delays in being tested for antibodies (median, 3 vs 0.5 and 1 year;P <.001). Individuals with GAD65 antibodies were more likely to develop SPS (27 [51.9%] of 52) or overlapping syndromes (8 [15.4%] of 52) than individuals with GlyR antibodies (5 [22.7%] and 0 CTNND1 [0%] of 22, respectively), who more often developed SPS-plus (12 [54.5%] of 22 vs 7 [13.5%] in Ambrisentan (BSF 208075) those with GAD65 antibodies); antibody-negative individuals experienced an intermediate syndrome distribution. In multivariable analysis, symptom severity (P= .001) and immunologic group (P= .01) were independently associated with end result. Compared with individuals with GlyR antibodies, those with GAD65 antibodies (odds percentage, 11.1,95% CI, 2.353.7;P= .003) had worse end result. Individuals without antibodies experienced similar Ambrisentan (BSF 208075) end result than individuals with GlyR antibodies (odds percentage, 4.2,95% CI, 0.920.0;P =.07). == CONCLUSIONS AND RELEVANCE == In SPSD, sign severity and presence and type of antibodies are predictors of end result. Stiff-person syndrome (SPS) is a disorder characterized by fluctuating muscle mass rigidity and painful spasms that happen spontaneously or are induced by varied stimuli.1,2Partial or segmental forms of the disorder, such as stiff-limb syndrome (SLS) and the more severe disease called progressive encephalomyelitis with rigidity and myoclonus (PERM), are usually considered within the spectrum of SPS, 36but there is an increasing recognition of atypical and overlapping syndromes. For all these disorders, which we collectively termedstiff-person spectrum disorder(SPSD), there is evidence of underlying immune mechanisms that target proteins mainly expressed by the inhibitory synapses. Six autoantigens have been identified, including glutamic acid decarboxylase (GAD65),7,8the 1-subunit of the glycine receptor (GlyR),9,10amphiphysin,11gephyrin,12dipeptidyl peptidase-like protein 6 (DPPX),13,14and the -aminobutyric acid-A (GABA-A) receptor (GABAaR).15Some of these immune responses have been suggested to be associated with distinct variants of SPSD,16but the degree of syndrome specificity and implications for treatment and prognosis are unclear. Because some autoantigens were recently discovered and SPS is usually a rare disease, most studies have focused on a limited number of autoantibodies (GAD65 or GlyR) and well-defined syndromes (SPS or PERM) without examining the entire spectrum of clinical-immunologic associations and the implications of being antibody negative. To address these issues, we investigated the clinical features of 121 patients with SPSD, decided the presence of autoantibodies to 8 potential targets of the inhibitory synapse, and compared the syndromes among the Ambrisentan (BSF 208075) most frequent immunophenotypes. In addition, we provide the treatment, outcome, and prognostic factors of 75 patients for whom long-term follow-up information was available. == Methods == == Study Design and Participants == We retrospectively reviewed the clinical information of patients with SPSD seen by us (57 cases) or whose serum or cerebrospinal fluid (CSF) samples were referred to our laboratory for antibody testing from January 1,1998, through December 31,2014. Data analysis was performed from July 1, 2015, through November 1, 2015. Stiff-person spectrum disorder was clinically defined by the presence of symptoms of axial stiffness and muscle spasms not restricted to the classic presentation of SPS but also including forms with partial or distal limb distribution or symptoms of encephalomyelitis. Clinical information was obtained by us or the referring physicians with a structured questionnaire..