Antiganglioside antibody frequency in routine clinical care settings.

BACKGROUND AND PURPOSE: Antiganglioside antibodies (AGAs) might be involved in the etiopathogenesis of many neurological diseases, such as Miller-Fisher syndrome (MFS) and Guillain-Barré syndrome (GBS). Available comprehensive reference data regarding AGA positivity rates and cross-responsiveness among AGAs (where one line immunoblot is positive for ≥1 AGA) during routine clinical care are scant. METHODS: In this 10-year monocentric retrospective study, 3560 immunoglobulin (Ig) G and IgM line blots (GA Generic Assays' Anti-Ganglioside Dot kit) obtained using cerebrospinal fluid (CSF) and serum samples from 1342 patients were analyzed for AGA positivity in terms of 14 diagnosis categories and AGA cross-responsiveness. RESULTS: Of all 3560 line blots 158 (4.4%) and of all CSF samples 0.4% (4/924) CSF line blots were AGA positive. For serum IgG, blots with positivity rates higher than the standard deviation of 15.6% were associated with MFS (GD3, GD1a, GT1a and GQ1b) and acute motor axonal neuropathy (AMAN) (GM1, GD1a and GT1a). For serum IgM, blots with positivity rates higher than the standard deviation of 8.1% were associated with AMAN (GM2, GT1a and GQ1b), MFS (GM1, GT1a and GQ1b), multifocal motor neuropathy (MMN) (GM1, GM2 and GQ1b) and chronic inflammatory demyelinating polyneuropathy (CIDP) (GM1). Cross-responsiveness was observed in 39.6% of all positive serum AGA. CONCLUSIONS: Testing for AGAs during routine clinical care rarely led to positive findings, both in serum and even less in CSF, except for the diagnoses AMAN, MFS, MMN and CIDP. Nonspecific findings found as cross-responsiveness between different AGA samples occur frequently, impacting the positivity of most AGA subtypes.

Anti-sulfatide antibodies in neurological disorders: should we test?

OBJECTIVE: Neurological autoimmune peripheral and central nervous system disorders can be associated with anti-sulfatide antibodies. These antibodies are considered potential diagnostic biomarkers, although their additional diagnostic value in neurological fields has been increasingly questioned. Given the little evidence of anti-sulfatide antibodies' frequency and diagnostic value in neurology, we aimed to fill this knowledge gap by investigating 10 years of data. METHODS: This retrospective study analyzed the results of the anti-ganglioside dot kits (GA Generic Assays GmbH) from 1318 serum samples and 462 cerebrospinal fluid (CSF) samples for the frequency, sensitivity, and specificity of anti-sulfatide antibodies in neurological disorders. RESULTS: Although anti-sulfatide antibodies are rarely present in neurological autoimmune disorders (serum IgM 2.5%, IgG 4.6%), they are also present in non-autoimmune diseases (serum IgM 1.2%, IgG 2.5%) and lack sensitivity and specificity towards being a diagnostic marker. Furthermore, anti-sulfatide antibodies are rarely found in CSF (e.g., no positive results for IgM), and including so-called borderline results ((+)) increases sensitivity and the false-positive rate in serum and CSF. DISCUSSION: While anti-sulfatide antibodies appear more frequently in neurological autoimmune diseases, they are rare overall and provide very limited diagnostic value in determining specific neurological diseases and-more importantly-if a neurological disease has a potential autoimmune etiology.

Myositis -specific and -associated antibodies in neurological disorders - A retrospective study of 727 patients.

OBJECTIVE: Myositis-specific antibodies (MSAs) and myositis-associated antibodies (MAAs) are assessed in clinical neurology, serving as a non-invasive tool for the differential diagnosis of autoimmune myopathies. However, the presence of MSAs and MAAs in neurological disorders remains uncertain. METHODS: Retrospective analysis was conducted on 878 serum samples from the neurological laboratory of the University Hospital Tübingen, Germany. The EUROLINE Myositis Profil 3 (IgG) Line Blot was used for antibody evaluation (anti-Mi2, -Ku, -PM-Scl100, -PM-Scl75, -Jo1, -SRP, -PL7, -PL12, -EJ, -OJ, and -Ro52). Samples were categorized into 19 disease groups, with consideration for myositis-linked and non-myositis-linked diseases. Then, the distribution of positive findings and the concurrent presence of more than one MAA/MSA were analyzed. RESULTS: Among 727 included line blots, 84 could be assigned to myositis-linked diseases (thereof 44 positive for MAA/MSA). MAA and MSA taken together were more frequently positive for the main group of myositis-linked disease (52.4 %) compared to the non-myositis-linked group (14.6 %, overall specificity 85.4 %). However, individual antibodies were specific, ranging above 97.5 %. False positive antibody results can also occur in neurological differential diagnoses such as muscle dystrophy or cramp fasciculation syndrome. Furthermore, the concurrent presence of more than one MAA/MSA does not show a significant association with the presence of a myositis-linked disease for antibody-positive samples (p = 0.136). DISCUSSION: Testing MSA and MAA simultaneously may not be suitable as a primary screening method for myositis-linked diseases in clinical neurological groups. However, MSAs and MAAs may offer valuable diagnostic support, particularly in cases where myositis is strongly considered.

Neurofilament light chain is a cerebrospinal fluid biomarker in hereditary spastic paraplegia.

OBJECTIVE: Despite the need for diagnostics and research, data on fluid biomarkers in hereditary spastic paraplegia (HSP) are scarce. We, therefore, explore Neurofilament light chain (NfL) levels in cerebrospinal fluid (CSF) of patients with hereditary spastic paraplegia and provide information on the influence of demographic factors. METHODS: The study recruited 59 HSP cases (33 genetically confirmed) and 59 controls matched in age and sex. Neurofilament light chain levels were assessed by enzyme-linked immunosorbent assay. The statistical analysis included the effects of age, sex, and genetic status (confirmed vs. not confirmed). RESULTS: Levels of CSF NfL were significantly increased in patients with hereditary spastic paraplegia compared to controls (median 741 pg/mL vs. 387 pg/mL, p < 0.001). Age (1.4% annual increase) and male sex (81% increase) impacted CSF NfL levels in patients. The age-dependent increase of CSF NfL levels was steeper in controls (2.6% annual increase). Thus, the CSF NfL ratio of patients and matched controls-expressing patients' fold increases in CSF NfL-declined considerably with age. INTERPRETATION: CSF NfL is a reliable cross-sectional biomarker in hereditary spastic paraplegia. Sex is a relevant factor to consider, as male patients have remarkably higher CSF NfL levels. While levels also increase with age, the gap between patients and controls is narrowing in older subjects. This indicates distinct temporal dynamics of CSF NfL in patients with hereditary spastic paraplegia, with a rise around phenotypic conversion and comparatively static levels afterward.