Autoimmunity to Gephyrin in Stiff-Man Syndrome

Background: Intrathecal synthesis of oligoclonal IgG antibodies against measles virus (MeV), varicella zoster virus (VZV) and herpes simplex virus type‐1 (HSV‐1) is a characteristic feature multiple sclerosis (MS). Methods: We have used isoelectric focusing‐immunoblot to define the clonal patterns of IgG and of IgG antibodies to MeV, VZV and HSV‐1 in supernatants of in vitro cultures of peripheral blood lymphocytes (PBL) and cerebrospinal fluid (CSF) cells and in sera and CSF from three patients with MS and three patients with clinically isolated syndromes (CIS) suspective of demyelinating disease. Results: In vitro synthesis of IgG by PBL was not detected in any patient. In contrast, in vitro synthesis by CSF cells of oligoclonal IgG and oligoclonal IgG antibodies to one or two of the three viruses tested was observed in all six patients. The clonal patterns of the in vitro synthesized IgG and virus specific IgG differed to varying extent from those synthesized intrathecally in vivo. However, in each patient, the in vitro and in vivo intrathecally produced antibodies displayed specificity for the same viruses. The addition of B cell activating factor (BAFF) had no effect on the amounts or clonal patterns of either total IgG or virus‐specific IgG produced by CSF cells in vitro. Conclusion: Virus specific B cells capable of spontaneous IgG synthesis are clonally expanded in the CSF of patients with MS. The B‐cell repertoire in CSF samples is only partially representative of the intrathecal B‐cell repertoire.

show abstract

“…Such patients have been reported to have more prominent stiffness in neck and arms than other SPS patients Butler 2000).…”

Section: Clinical Presentationmentioning

confidence: 90%

“…Also, an antibody to glycine receptors has been identified in a patient with PER (Hutchinson 2008). In paraneoplastic variants SPS, antibodies are directed against two other proteins in the GABAergic and glycinergic synapses; amphiphysin and gephyrin Butler 2000).…”

Section: Other Aspects Of Autoimmunity In Spsmentioning

confidence: 99%

MS and clinically isolated syndromes: Shared specificity but diverging clonal patterns of virus‐specific IgG antibodies produced in vivo and by CSF B cells in vitro

Skorstad

Vandvik

Vartdal

et al. 2009

Euro J of Neurology

View full text Add to dashboard Cite

show abstract

“…Pain, which is localized in the areas in which rigidity is observed, is persistent and worsening of pain might sometimes be the first symptom (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). Pain that is localized in the low back is associated with an increased lumbar lordosis and concomitant muscle spasms because of paraspinal muscle rigidity.…”

Section: Discussionmentioning

confidence: 99%

“…Five percent of patients have been reported to have the paraneoplastic condition (1,3,6,8). In some cases that develop with neoplasms, such as breast cancer, anti-amphiphiles or anti-gephyrin autoantibody positivity has been reported (9,10).…”

Section: Introductionmentioning

confidence: 99%

A Stiff Person Case Admitted Phsysical Medicine and Rehabilitation Outpatient Clinic with Low Back Pain

Karaoğlan¹,

Ote²,

Koseoglu³

et al. 2015

Turk J Phys Med Rehab

View full text Add to dashboard Cite

Stiff-Person Syndrome (SPS) is a rare disorder that is characterized by stiffness and rigidity of the axial, abdominal, and extremity muscles. It is associated with several autoimmune diseases or paraneoplastic conditions. We report a case of SPS with Hashimoto's thyroiditis who complained of low back pain. Her physical examination was remarkable in that her abdominal and axial muscles were firm to palpation, and she had hyperlordosis of the spine. Active range of motion of the spine was limited, and she had a robotic gait. Electromyography demonstrated continuous motor unit activity in the agonist and antagonist muscles. Diagnosis of SPS was confirmed because antiglutamic acid decarboxylase was present in the cerebrospinal fluid. She favorably responded to intravenous administration of immunoglobulin, diazepam, and baclofen and stretching, strengthening, and range of motion exercises.

show abstract

“…Other autoantibodies associated with SPS include those to the GABA-A receptor, amphiphysin, and gephyrin [303][304][305][306]. Patients with progressive encephalopathy associated with limb rigidity are said to have progressive encephalomyelitis with rigidity and myoclonus (PERM) or stiff-person plus syndrome.…”

Section: Stiff-person Syndromementioning

confidence: 99%

Immune Mediated Diseases and Immune Modulation in the Neurocritical Care Unit

Geldern¹,

McPharlin

Becker

2012

Neurotherapeutics

View full text Add to dashboard Cite

This chapter will review the spectrum of immunemediated diseases that affect the nervous system and may result in an admission to the neurological intensive care unit. Immunomodulatory strategies to treat acute exacerbations of neurological diseases caused by aberrant immune responses are discussed, but strategies for long-term immunosuppression are not presented. The recommendations for therapeutic intervention are based on a synthesis of the literature, and include recommendations by the Cochrane Collaborative, the American Academy of Neurology, and other key organizations. References from recent publications are provided for the disorders and therapies in which randomized clinical trials and large evidenced-based reviews do not exist. The chapter concludes with a brief review of the mechanisms of action, dosing, and side effects of commonly used immunosuppressive strategies in the neurocritical care unit.

show abstract

Autoimmunity to Gephyrin in Stiff-Man Syndrome

Cited by 188 publications

References 42 publications

MS and clinically isolated syndromes: Shared specificity but diverging clonal patterns of virus‐specific IgG antibodies produced in vivo and by CSF B cells in vitro

MS and clinically isolated syndromes: Shared specificity but diverging clonal patterns of virus‐specific IgG antibodies produced in vivo and by CSF B cells in vitro

A Stiff Person Case Admitted Phsysical Medicine and Rehabilitation Outpatient Clinic with Low Back Pain

Immune Mediated Diseases and Immune Modulation in the Neurocritical Care Unit

Contact Info

Product

Resources

About