Anti‐NDMA receptor (NMDAR) encephalitis is an auto‐immune condition. There is no uniformly agreed treatment strategy for the disorder in children. We report the use of intrathecal treatment with ...methotrexate and methylprednisolone in three children (one male, two females, age 10y, 11y, and 14y) with anti‐NMDAR encephalitis, who did not respond to steroids, plasmapheresis, or rituximab. There was significant clinical improvement and stabilization of the anti‐NMDAR antibody titers in cerebrospinal fluid (CSF) and blood in two patients. In the third patient, although anti‐NMDAR antibody titers in CSF decreased, clinical recovery was less satisfactory. Intrathecal treatment with methotrexate and methylprednisolone seems to be a promising alternative treatment for some paediatric cases of resistant anti‐NMDAR encephalitis.
This article is commented on by Byrne and Lim on pages 14–15 of this issue.
Background
Myelin oligodendrocytes glycoprotein (MOG) antibody-associated disease (MOGAD) represent 25% of pediatric acquired demyelinating syndrome (ADS); 40% of them may relapse, mimicking multiple ...sclerosis (MS), a recurrent and neurodegenerative ADS, which is MOG-Abs negative.
Aims
To identify MOG antigenic immunological response differences between MOGAD, MS and control patients, and between relapsing
versus
non-relapsing subgroups of MOGAD.
Methods
Three groups of patients were selected: MOGAD (n=12 among which 5 relapsing (MOGR) and 7 non-relapsing (MOGNR)), MS (n=10) and control patients (n=7). Peripheral blood mononuclear cells (PBMC) collected at the time of the first demyelinating event were cultured for 48 h with recombinant human (rh)-MOG protein (10 μg/ml) for a specific stimulation or without stimulation as a negative control. The T cells immunophenotypes were analyzed by flow cytometry. CD4
+
T cells, T helper (Th) cells including Th1, Th2, and Th17 were analyzed by intracellular staining of cytokines. Regulatory T cells (T
regs
, Foxp3
+
), CD45RA
-
Foxp3
+
T
regs
and subpopulation naive T
regs
(CD45RA
+
Foxp3
int
), effector T
regs
(CD45RA
-
Foxp3
high
) and non-suppressive T
regs
(CD45RA
-
Foxp3
int
) proportions were determined.
Results
The mean onset age of each group, ranging from 9.9 to 13.8, and sex ratio, were similar between MOGR, MOGNR, MS and control patients as analyzed by one-way ANOVA and Chi-square test. When comparing unstimulated to rh-MOG stimulated T cells, a significant increase in the proportion of Th2 and Th17 cells was observed in MOGAD. Increase of Th17 cells was significant in MOGNR (means: 0.63 ± 0.15
vs.
1.36 ± 0.43; Wilcoxon-test
p
= 0.03) but not in MOGR. CD4
+
T
regs
were significantly increased in MOGNR (means: 3.51 ± 0.7
vs.
4.59 ± 1.33; Wilcoxon-test
p
= 0.046) while they decreased in MOGR. CD45RA
-
Foxp3
+
T
regs
were significantly decreased in MOGR (means: 2.37 ± 0.23
vs.
1.99 ± 0.17; paired t-test
p
= 0.021), but not in MOGNR. MOGR showed the highest ratio of effector T
regs
/non suppressive-T
regs,
which was significantly higher than in MOGNR.
Conclusions
Our findings suggest that CD4
+
Th2 and Th17 cells are involved in the pathophysiology of MOGAD in children. The opposite response of T
regs
to rh-MOG in MOGNR, where CD4
+
T
regs
increased, and in MOGR, where CD45RA
-
Foxp3
+
T
regs
decreased, suggests a probable loss of tolerance toward MOG autoantigen in MOGR which may explain relapses in this recurrent pediatric autoimmune disease.
Autoantibodies against myelin oligodendrocyte glycoprotein (anti-MOG-Abs) occur in a majority of children with acquired demyelinating syndromes (ADS) and physiopathology is still under investigation. ...As cynomolgus macaques immunized with rhMOG, all develop an experimental autoimmune encephalomyelitis (EAE), we assessed relatedness between anti-MOG-Abs associated diseases in both species.
The study includes 27 children followed for ADS and nine macaques with rhMOG-induced EAE. MRI lesions, cytokines in blood, and CSF at onset of ADS or EAE, as well as histopathological features of brain lesions were compared.
Twelve children with anti-MOG-Abs ADS (ADS MOG+) and nine macaques with EAE, presented increased IL-6 and G-CSF in the CSF, whereas no such signature was found in 15 ADS MOG-. Furthermore, IgG and C1q were associated to myelin and phagocytic cells in brains with EAE (n = 8) and in biopsies of ADS MOG+ (n = 2) but not ADS MOG- children (n = 1). Macaque brains also revealed prephagocytic lesions with IgG and C1q depositions but no leukocyte infiltration.
Children with ADS MOG+ and macaques with EAE induced with rhMOG, present a similar cytokine signature in the CSF and a comparable aspect of brain lesions indicating analogous pathophysiological processes. In EAE, prephagocytic lesions points at IgG as an initial effector of myelin attack. These results support the pertinence of modeling ADS MOG+ in non-human primates to apprehend the natural development of anti-MOG-associated disease, find markers of evolution, and above all explore the efficacy of targeted therapies to test primate-restricted molecules.
In this retrospective study, we aimed at defining the clinical, paraclinical and outcome features of acute neurological syndromes associated with anti-GQ1b antibodies.
We identified 166 patients with ...neurological symptoms appearing in less than 1 month and anti-GQ1b antibodies in serum between 2012 and 2022. Half were female (51%), mean age was 50 years (4-90), and the most frequent clinical features were areflexia (80% of patients), distal upper and lower limbs sensory symptoms (78%), ophthalmoplegia (68%), sensory ataxia (67%), limb muscle weakness (45%) and bulbar weakness (45%). Fifty-three patients (32%) presented with complete (21%) and incomplete (11%) Miller Fisher syndrome (MFS), thirty-six (22%) with Guillain-Barre syndrome (GBS), one (0.6%) with Bickerstaff encephalitis (BE), and seventy-three (44%) with mixed MFS, GBS & BE clinical features. Nerve conduction studies were normal in 46% of cases, showed demyelination in 28%, and axonal loss in 23%. Anti-GT1a antibodies were found in 56% of cases, increased cerebrospinal fluid protein content in 24%, and Campylobacter jejuni infection in 7%. Most patients (83%) were treated with intravenous immunoglobulins, and neurological recovery was complete in 69% of cases at 1 year follow-up. One patient died, and 15% of patients relapsed. Age > 70 years, initial Intensive Care Unit (ICU) admission, and absent anti-GQ1b IgG antibodies were predictors of incomplete recovery at 12 months. No predictors of relapse were identified.
This study from Western Europe shows acute anti-GQ1b antibody syndrome presents with a large clinical phenotype, a good outcome in 2/3 of cases, and frequent relapses.
ObjectivesWe aimed to compare disease characteristics between primary Sjögren’s syndrome (pSS) patients of African ancestry (AA) and Caucasian ancestry.MethodsWe conducted a retrospective, ...case–control study in a French national and European referral centre for pSS. All patients with pSS of AA were matched with two Caucasians patients having similar follow-up duration. We explored clinical and biological parameters associated with a cumulative EULAR Sjögren’s Syndrome Disease Activity Index (cumESSDAI ≥5) (consisting of individual clinESSDAI domain maximum throughout follow-up).ResultsWe identified 74 patients of AA matched with 148 Caucasian. Median age at pSS diagnosis was younger in AA patients (43 years (IQR 33–51) vs 56 years (44.8–59.2), p<0.001). AA patients presented higher median titre of gammaglobulins (18.5 g/L (IQR 15–22.8) vs 13.4 g/L (9.9–16.9), p<0.001), more frequently positive for anti-SSA (88% vs 72%, p=0.007) and anti-RNP (11% vs 2.7%, p=0.023) antibodies. During the follow-up (median: 6 years (IQR 2–11)), AA patients presented more systemic complications: arthritis, myositis, interstitial lung disease, lymphadenopathy, central nervous system involvement. Median cumESSDAI score was higher in AA patients (7.5 (IQR 3.2–16.0) vs 4.0 (IQR 2.0–9.0), p=0.002). Interestingly, in multivariate analyses, factors associated with disease activity were sub-Saharan AA (OR 2.65 (95% CI 1.06 to 6.94)), rheumatoid factor (OR 2.50 (95% CI 1.28 to 4.96)) and anti-RNP positivity (OR 11.1 (95% CI 1.88 to 212)).ConclusionPatients of AA display higher disease activity with a hallmark of higher B-cell activation. Studies to investigate biological drivers behind such differences are needed.
Since plasmablasts and plasma cells are recognised as essential drivers of disease activity in SjD, present in the salivary glands and part of the cell signature of the disease,1 they could be a ...promising therapeutic target. The search for antiglycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 (GPIHBP1) was positive at high titre (6121 U/mL, threshold of positivity=57 U/mL) leading to the diagnosis of autoimmune hyperchylomicronemia complicating SjD.2 Hyperchylomicronaemia is characterised by marked accumulation of chylomicrons in the plasma, and elevated triglyceride (TG) levels exceeding 10 g/L with high risk of acute pancreatitis. Vasculitis relapsed with flare of purpura and reappearance of proteinuria with a protein/creatinine ratio at 650 mg/g and of cryoglobulin despite these different lines of treatment. ...we decided to treat the patient with daratumumab with the same protocol as for patient 1.
Anti-signal recognition particle (SRP) antibodies are important serological markers for the diagnosis and the prognosis of idiopathic inflammatory myopathy (IIM), especially to distinguish ...immune-mediated necrotizing myopathy (IMNM). This study was set up to investigate the phenotype associated with anti-SRP antibodies and to evaluate the methods for detecting these antibodies. Clinical and biological data were retrospectively obtained from 60 adult patients with anti-SRP antibodies detected by a dot immunoassay from 12 centers. Thirty-six (60 %) out of these 60 patients suffered from an IIM, and among them, 21 patients were diagnosed as IMNM. Among patients with a definite IIM, proximal weakness and myalgia were prominent symptoms at the time of diagnosis. Only few patients displayed severe extra-muscular symptoms such as cardiac involvement or severe myositis. Mean creatine kinase levels were high for all patients except for two of them. When testing by indirect immunofluorescence (IIF) on HEp2 cells, the fraction of patients displaying the typical anti-SRP fine speckled staining of the cytoplasm was higher in patients with IIM (30/36) (83 %) than in patients with non-IIM (3/24) (12.5 %) (
p
< 0.0001). Thirty (91 %) out of 33 patients with a positive immunodot and a characteristic IIF cytoplasmic staining suffered from a clinical definite myositis, whereas only 6 (22 %) out of 27 patients with a positive immunodot but a negative cytoplasmic pattern suffered from a myositis (
p
< 0.00001). This series highlights the strong heterogeneity of anti-SRP positivity that encompassed IMNM and non-IMNM and supports the necessity of considering both IIF and dot immunoassay to confirm the diagnosis of anti-SRP-associated myositis.
Accreditation of an in vitro diagnostic assay according to the NF/EN/ISO 15189 standard requires to analyze its technical performance before implementation for routine use, and annually when ...reviewing effectiveness of quality controls. Performance is evaluated through repeatability, intermediate fidelity, accuracy and uncertainty of measurement. The coefficients of variation (CV) of the intra-assay and inter-assay precision tests must be compared with those of "peers" (results from laboratories employing the same method) and also with those obtained with "all methods", i.e., results from all laboratories performing the same assay, irrespective of the method. To our best knowledge, there is currently no French or international recommendation on what the acceptable limits of performance for specific IgE and tryptase assays should be. Therefore, the AllergoBioNet network of hospital allergy laboratories set out to characterize the performance of their current methods as a basis for the development of recommendations. The results provided by 24 centers were analyzed and led to consensus recommendations for specific IgE, total IgE and tryptase assays.
PDF
