scholarly journals The MRZ-Reaction and Specific Autoantibody Detection for Differentiation of ANA-Positive Multiple Sclerosis From Rheumatic Diseases With Cerebral Involvement

2019 ◽  
Vol 10 ◽  
Author(s):  
Nils Venhoff ◽  
Jens Thiel ◽  
Marta Rizzi ◽  
Ana Venhoff ◽  
Sebastian Rauer ◽  
...  
BMC Neurology ◽  
2018 ◽  
Vol 18 (1) ◽  
Author(s):  
Tilman Hottenrott ◽  
Rick Dersch ◽  
Benjamin Berger ◽  
Dominique Endres ◽  
Daniela Huzly ◽  
...  

Author(s):  
Sudarshini Ramanathan ◽  
Adam Al-Diwani ◽  
Patrick Waters ◽  
Sarosh R. Irani

Abstract The autoimmune encephalitis (AE) syndromes have been characterised by the detection of autoantibodies in serum and/or cerebrospinal fluid which target the extracellular domains of specific neuroglial antigens. The clinical syndromes have phenotypes which are often highly characteristic of their associated antigen-specific autoantibody. For example, the constellation of psychiatric features and the multi-faceted movement disorder observed in patients with NMDAR antibodies are highly distinctive, as are the faciobrachial dystonic seizures observed in close association with LGI1 antibodies. These typically tight correlations may be conferred by the presence of autoantibodies which can directly access and modulate their antigens in vivo. AE remains an under-recognised clinical syndrome but one where early and accurate detection is critical as prompt initiation of immunotherapy is closely associated with improved outcomes. In this review of a rapidly emerging field, we outline molecular observations with translational value. We focus on contemporary methodologies of autoantibody detection, the evolution and distinctive nature of the clinical phenotypes, generalisable therapeutic paradigms, and finally discuss the likely mechanisms of autoimmunity in these patients which may inform future precision therapies.


2003 ◽  
Vol 143 (1-2) ◽  
pp. 60-64 ◽  
Author(s):  
M. Ban ◽  
S.J. Sawcer ◽  
R.N.S. Heard ◽  
B.H. Bennetts ◽  
S. Adams ◽  
...  

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2543
Author(s):  
Tilman Robinson ◽  
Ahmed Abdelhak ◽  
Tanima Bose ◽  
Edgar Meinl ◽  
Markus Otto ◽  
...  

The MRZ reaction (MRZR) comprises the three antibody indices (AIs) against measles, rubella, and varicella zoster virus, reflecting an intrathecal polyspecific B cell response highly specific for multiple sclerosis (MS). Thus, MRZR can be used to confirm a diagnosis of primary progressive MS (PPMS) but its pathophysiological and wider clinical relevance is unclear. This study aimed to investigate whether PPMS patients with a positive MRZR (MRZR+) differ from those with a negative MRZR (MRZR-) according to cerebrospinal fluid (CSF) biomarkers of B cell activity, neuroaxonal damage or glial activity, and clinical features. (1) Methods: In a multicenter PPMS cohort (n = 81) with known MRZR status, we measured B cell-activating factor (BAFF), chemokine CXC ligand 13 (CXCL-13), soluble B cell maturation antigen (sBCMA), soluble transmembrane activator and CAML interactor (sTACI), and chitinase-3-like protein 1 (CHI3L1) in the CSF with enzyme-linked immunosorbent assays (ELISAs). Glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) were detected in serum and CSF using single molecule array (SIMOA) technology. (2) Results: MRZR+ patients (45.7% of all PPMS patients) revealed higher levels of NfL in CSF compared to MRZR- patients (54.3%). There were positive correlations between each of sBCMA, sTACI, and intrathecal immunoglobin G (IgG) synthesis. Additionally, NfL concentrations in serum positively correlated with those in CSF and those of GFAP in serum. However, MRZR+ and MRZR- patients did not differ concerning clinical features (e.g., age, disease duration, Expanded Disability Status Scale (EDSS) at diagnosis and follow-up); CSF routine parameters; CSF concentrations of BAFF, CXCL-13, sBCMA, sTACI, CHI3L1, and GFAP; or serum concentrations of GFAP and NfL. (3) Conclusions: In PPMS patients, MRZR positivity might indicate a more pronounced axonal damage. Higher levels of the soluble B cell receptors BCMA and transmembrane activator and CAML interactor (TACI) in CSF are associated with a stronger intrathecal IgG synthesis in PPMS.


2015 ◽  
Vol 38 (6) ◽  
Author(s):  
Karsten Conrad ◽  
Nadja Röber ◽  
Sebastian Rudolph ◽  
Michael Mahler

AbstractDespite the progress in the establishment of specific autoantibody assays, screening for antinuclear antibodies (ANA) by indirect immunofluorescence on HEp-2 cells for quality-oriented laboratory diagnosis of ANA associated rheumatic diseases (AARD) remains indispensable. Research results on the relevance of the dense fine speckled (DFS) pattern and DFS70 antibodies disclosed novel possibilities to optimize the serological stepwise diagnostics of AARD. The DFS pattern on HEp-2 cells is well differentiated from the classic “homogeneous” ANA pattern associated with dsDNA antibodies. In DFS pattern positive sera the most important detectable ANA specificity is the DFS70 antibody (synonym LEDGF antibody). This antibody is also the most frequent ANA specificity in ANA positive healthy persons. The prevalence of DFS70 antibodies in AARD patients is significantly lower compared with the prevalence in ANA-positive healthy individuals. There is a negative association between DFS70 antibodies and AARD, especially if no concomitant AARD-specific autoantibodies are found. Isolated DFS70 antibodies are detectable in <1% of AARD, but are detectable in 5%–11% of healthy individuals. In the presence of an isolated DFS70 antibody, the posttest probability for AARD is reduced significantly. DFS70 antibodies are valuable novel biomarkers for the improved interpretation of positive ANA but without detectable AARD associated autoantibodies and should be integrated in modified test algorithms to avoid unnecessary referrals and examinations of ANA-positive subjects.


Author(s):  
Farshid Mashayekhi ◽  
Saeed Sadigh-Eteghad ◽  
Amirreza Naseri ◽  
Milad Asadi ◽  
Negin Abbasi Garravnd ◽  
...  

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