Emboldened antigens had were significantly associated with GBS versus healthy controls following Bonferroni correction, italicised antigens were significant only following less stringent Benjamini and Hochberg step-up correction for multiple comparisons
Emboldened antigens had were significantly associated with GBS versus healthy controls following Bonferroni correction, italicised antigens were significant only following less stringent Benjamini and Hochberg step-up correction for multiple comparisons.. binding intensities of each component glycolipid. Any residual intensity indicates complex enhanced binding. As before, GBS sera lie above and healthy control (HC) sera below the horizontal white line. The same colour scale as Figure S1 has been Boc-NH-PEG2-C2-amido-C4-acid used.(TIF) pone.0082337.s003.tif (2.8M) GUID:?B2BE6344-F7E4-49F3-A351-72D3F40E0A8D Table S1: Diagnoses of patients with other neurological diseases used as controls. ONND C other noninflammatory neurological diseases, MS C multiple sclerosis, RR C relapsing remitting, PP C primary progressive, SP C secondary progressive, CIS C clinically isolated syndrome, TM C transverse myelitis, CFS C chronic fatigue syndrome, IIH C idiopathic intracranial hypertension, CVD C cerebrovascular disease, PFO C patent foramen ovale, CVST C cerebral venous sinus thrombosis.(DOCX) pone.0082337.s004.docx (15K) GUID:?EBFB0D35-5052-40A3-A0A8-EB722D6CC226 Abstract Autoantibodies are infrequently detected in the sera of patients with the demyelinating form of Guillain-Barr syndrome most commonly encountered in the Western world, despite abundant circumstantial evidence suggesting their existence. We hypothesised that antibody specificities reliant on Boc-NH-PEG2-C2-amido-C4-acid Boc-NH-PEG2-C2-amido-C4-acid the interactions of neighbouring membrane glycolipids could explain this discrepancy, and would not have been detected by traditional serological assays using highly purified preparations of single gangliosides. To assess the frequency of glycolipid complex antibodies in a Western European cohort of patients GBS we used a newly developed combinatorial glycoarray methodology to screen against large range of antigens (11 gangliosides, 8 other single glycolipids and 162 heterodimeric glycolipid complexes). Serum samples of 181 patients from a geographically defined, Western European cohort of GBS cases were analysed, along with 161 control sera. Serum IgG binding to single gangliosides was observed in 80.0% of axonal GBS cases, but in only 11.8% of cases with demyelinating electrophysiology. The inclusion of glycolipid complexes increased the positivity rate in demyelinating disease to 62.4%. There were 40 antigens with statistically significantly increased binding intensities in GBS as compared to healthy control sera. Fertirelin Acetate Of these, 7 complex antigens and 1 single ganglioside also produced statistically significantly increased binding intensities in GBS versus neurological disease controls. The detection of antibodies against specific complexes was associated with particular clinical features including disease severity, requirement for mechanical ventilation, and axonal electrophysiology. This study demonstrates that while antibodies against single gangliosides are often found in cases with axonal-type electrophysiology, antibodies against glycolipid complexes predominate in cases with demyelinating electrophysiology, providing a more robust serum biomarker than has ever been previously available for such cases. This work confirms the activation of the humoral immune system in the dysimmune disease process in GBS, and correlates patterns of antigen recognition with different clinical features. Introduction Current evidence suggests that Guillain-Barr syndrome (GBS) Boc-NH-PEG2-C2-amido-C4-acid is caused in some cases by autoantibodies arising via microbial molecular mimicry [1C4]. Certain antibodies clearly correlate with particular disease subtypes  ; however, these clinical-serological relationships are not absolute. GBS cohorts dominated by demyelinating/AIDP-type electrophysiology have no prevalent antibody association, and no serum biomarker is available to reliably support diagnosis [7,8]. Furthermore, there are inconsistencies between the ganglioside Boc-NH-PEG2-C2-amido-C4-acid antigen tissue distribution and disease phenotype , leading some to debate the pathological significance of detected antibodies [10,11]. In addition to serological reactions with single ganglioside or glycolipid species, it has recently been observed that certain GBS-associated autoantibodies may only bind to ganglioside complexes (GSC). GSC antibodies react with mixtures of two different gangliosides, whilst failing to recognise either component ganglioside alone, [12,13]. This concept builds on the.