Treatment of non-systemic Sjögren's syndrome: Potential prevention of systematization with immunosuppressant agent/biotherapy.

Sjögren's syndrome (SS) is a systemic autoimmune pathology manifested mainly by a dry syndrome, intense asthenia and arthromyalgia. Systemic manifestations may also occur. Since 2019, immunosuppressant agents (IS) or biotherapies are recommended only for patients with systemic involvement. However, before 2019, in some cases, paucisymptomatic patients had been treated with IS/biotherapies, often off-label. Objective: We propose to evaluate the benefit and safety of using IS/biotherapy in patients with SS without systemic involvement. Methods: We retrospectively collected the clinical records of all patients with SS diagnosed according to ACR/EULAR diagnostic criteria followed up between January 1980 and October 2023 at Grenoble University Hospital (France). Results: Eighty-three patients were included: 64 with an initially non-systemic form. Of these patients with an initially non-systemic form, 24 were treated with IS/biotherapy. None of them developed secondary systematization, whereas 11 out of 40 patients in the untreated group did (p < 0.05). On the other hand, IS/biotherapy did not appear to improve dry syndrome. There were no serious adverse events. Conclusion: Early introduction of an IS/biotherapy treatment appears to provide a benefit for the patient without side effects.

Heterogeneity of antibody-secreting cells infiltrating autoimmune tissues.

The humoral response is frequently dysfunctioning in autoimmunity with a frequent rise in total serum immunoglobulins, among which are found autoantibodies that may be pathogenic by themselves and/or propagate the inflammatory reaction. The infiltration of autoimmune tissues by antibody-secreting cells (ASCs) constitutes another dysfunction. The known high dependency of ASCs on the microenvironment to survive combined to the high diversity of infiltrated tissues implies that ASCs must adapt. Some tissues even within a single clinical autoimmune entity are devoid of infiltration. The latter means that either the tissue is not permissive or ASCs fail to adapt. The origin of infiltrated ASCs is also variable. Indeed, ASCs may be commonly generated in the secondary lymphoid organ draining the autoimmune tissue, and home at the inflammation site under the guidance of specific chemokines. Alternatively, ASCs may be generated locally, when ectopic germinal centers are formed in the autoimmune tissue. Alloimmune tissues with the example of kidney transplantation will also be discussed own to their high similarity with autoimmune tissues. It should also be noted that antibody production is not the only function of ASCs, since cells with regulatory functions have also been described. This article will review all the phenotypic variations indicative of tissue adaptation described so for at the level of ASC-infiltrating auto/alloimmune tissues. The aim is to potentially define tissue-specific molecular targets in ASCs to improve the specificity of future autoimmune treatments.

Anakinra reduces lung inflammation in experimental acute lung injury.

INTRODUCTION: Acute respiratory distress syndrome (ARDS) is a severe form of acute lung injury (ALI) resulting in life-threatening hypoxaemia. Although ARDS can be caused by a variety of pathogens or major trauma, it is best known as the major cause of mortality in COVID-19 patients. Since ARDS is often associated with dysregulated inflammatory immune responses, immunomodulatory approaches represent a possible treatment option. The objective of this study was to evaluate the therapeutic potential of interleukin (IL)-1 blockade using Anakinra in a mouse model of lipopolysaccharide (LPS)-induced ALI. METHODS: We evaluated the effects of a daily subcutaneous Anakinra treatment in a mouse model of LPS-induced ALI. We monitored body weight to assess the general health status of the mice. Two days after ALI induction, we evaluated the inflammatory cytokine MIP-2 as well as protein levels in bronchoalveolar lavage (BAL) fluids. Two and nine days after ALI induction, we evaluated infiltrating leukocytes in BAL fluid and lung tissue. RESULTS: Anakinra treatment reduced ALI-induced weight loss compared to nontreated groups. At Day 2, Anakinra treatment reduced levels of MIP-2 and protein in BAL fluids and reduced frequencies of NK cells and neutrophils in the lung tissue. Nine days after ALI induction, Anakinra treated mice displayed reduced levels of neutrophils and alveolar macrophages in BAL fluids. CONCLUSIONS: IL-1 blockade using Anakinra reduced classical hallmarks of inflammation in a mouse model of ALI. Our data support ongoing and future research on the evaluation of Anakinra as a potential treatment option in ARDS.

COVID-19 as a trigger of acute attacks in people with hereditary angioedema.

Acute attacks could occur during the convalescent phase of COVID-19 illness, more commonly in patients with a history of frequent attacks. However it is unclear whether the acute attacks during the convalescent phase are specifically triggered by COVID-19 or not.

Idiopathic Angioedema: Current Challenges.

The etiological diagnosis of isolated recurrent angioedema poses problems because it must often be done urgently. Angioedema secondary to nonspecific mast cell activation (MC-AE) is the most frequent form and is usually mild. Bradykinin mediated angioedema (BK-AE) is rarer but potentially fatal in the absence of the correct treatment. Few biological markers exist. The C1-inhibitor (C1-inh) functional assay can exclude AE due to C1-inh deficiency. Genetic diagnoses of hereditary AE due to abnormal C1-inh AE have progressed with four currently known mutations. However, determining the physiopathological mechanism leading to some isolated AE cases is sometimes very difficult. In such cases, therapeutic tests are then the only solution: antihistamines at high doses and omalizumab for suspected MC-AE, icatibant for suspected AE-BK. Identifying new markers would be a great help.

Screening of hepatitis E in patients presenting for acute neurological disorders.

INTRODUCTION: Hepatitis E virus (HEV) infection has been reported to be associated with neurological disorders. However, the real prevalence of acute hepatitis E in those diseases is still unknown. We determined the prevalence of anti-HEV IgM antibody in a population with acute non-traumatic, non-metabolic, non-vascular neurological injury. METHOD: A registry was created in Grenoble Hospital University from 2014 to 2018 to collect data on patients with acute (<3 months) non-traumatic, non-metabolic, non-vascular neurological injuries. Acute hepatitis E was defined as anti-HEV IgM-positive serum in immunocompetent patient, and as anti-HEV IgM-positive serum or HEV RNA-positive serum in immunocompromised patients. RESULTS: One hundred fifty-nine patients were included. Anti-HEV IgM seroprevalence in our cohort of non-traumatic, non-metabolic, non-vascular neurological injuries was 6.9% (eleven patients, including 4 Parsonage-Turner syndrome (PTS) and 2 Guillain-Barré syndrome (GBS)). Elevated transaminases were observed in only 64% of hepatitis E patients and cholestasis in 64%. CONCLUSION: In this study, 6·9% of patients with acute non-traumatic, non-metabolic, non-vascular neurological injuries had a probable recent HEV infection. HEV serology should be systematically performed in this population, even in patients with normal transaminase level.

Long-term outcomes in temporal lobe epilepsy with glutamate decarboxylase antibodies.

OBJECTIVE: To assess the long-term outcomes of patients with temporal lobe epilepsy and CSF anti-glutamate decarboxylase antibodies (GAD65-Abs). METHODS: We retrospectively analyzed the clinical records of 35 patients with temporal lobe epilepsy and CSF GAD65-Abs, collected from January 1993 to December 2016 and assessed cognitive impairment and seizure activity at last visit. Cognitive impairment was considered significant if impacting on daily life activities. Immunohistochemistry on rat brain slices and ELISA were used for antibody detection and titration. RESULTS: Median age was 30 years (range 2-63), 32/35 (91%) patients were female, and median follow-up was 68 months (range 7-232). At presentation, 20 patients had isolated temporal lobe epilepsy and 15 patients had other limbic symptoms, including anterograde amnesia (n = 10) and behavioral disturbances (n = 5). Progressive clinical deterioration over follow-up was reported in 28/35 patients (80%), including gradual increase of memory impairment (n = 25), and apparition of behavioral disturbances (n = 4) or mood disorders (n = 18). At last follow-up, 24/35 (69%) patients had cognitive disturbances with an impact on patient's daily life activities, and 28/35 (80%) still had active seizures. CONCLUSION: Most patients with temporal lobe epilepsy and CSF GAD65-Abs develop a chronic disease with progressive cognitive impairment and refractory epilepsy regardless of the presence of additional limbic symptoms at onset.

Multiplex family with GAD65-Abs neurologic syndromes.

OBJECTIVE: Neurologic autoimmune syndromes associated with anti-glutamate acid decarboxylase 65 antibodies (GAD65-Abs) are rare and mostly sporadic. METHODS: We describe a niece and her aunt with GAD65-Abs neurologic syndromes. High-resolution HLA typing of Class I and Class II alleles was performed using next-generation sequencing. RESULTS: The proband had cerebellar ataxia and probable limbic encephalitis features, whereas her niece had stiff-person syndrome. Both had a high titer of GAD65-Abs in serum and CSF and showed signs of inflammation in CSF. Both affected members carried the same rare recombinant DRB1*15:01:01∼DQA1*01:02:01∼DQB1*05:02:01 haplotype, which may or may not be involved in disease susceptibility. Of interest, other unaffected members of the family either had the same HLA haplotype but normal serum GAD65-Abs or had different HLA types but a high titer of serum GAD65-Abs without neurologic symptoms, suggesting cumulative effects. CONCLUSIONS: This unique association strengthens the concept that hereditary factors, possibly including specific HLA haplotypes, play a role in neurologic syndromes associated with GAD65-Abs.

Potentially stress-induced acute splanchnic segmental arterial mediolysis with a favorable spontaneous outcome.

A 62-year-old woman presented with hemithoracic anesthesia and acute abdominal pain following a violent psychological stress. Magnetic resonance imaging showed a thoracic hematoma with arachnoiditis of the spinal cord. Tomography revealed a typical aspect of segmental arterial mediolysis with multiple aneurysms and stenoses of the splanchnic arteries, confirmed by abdominal arteriography. There was no argument for hereditary, traumatic, atherosclerotic, infectious, or inflammatory arterial disease. Segmental arterial mediolysis was diagnosed on the basis of the radiologic data and probably involved both medullary and splanchnic arteries. The patient spontaneously recovered and was in good health 18 months later.

Hepatitis E and neuralgic amyotrophy: Five cases and review of literature.

Hepatitis E virus infection - mainly genotype 3 - is increasingly common in industrialized countries. Infection is usually asymptomatic, but cases of central or peripheral neurological symptoms with hepatitis E have been described. The most frequent is Guillain-Barre but somes cases of neuralgic amyotrophy have been described. In our center, since 2010, we have identified five cases of neuralgic amyotrophy associated with acute hepatitis E in immunocompetent patients. For all these patients, neuralgic amyotrophy was diagnosed with electromyogram and positive IgM for hepatitis E, and detectable HEV RNA in 4 of the cases. Including our patients, we count 26 cases in literature. The mean age of the patients was 44 years old, with a large predominance of males (88%). The disorder is bilateral and asymmetric in 69% of cases. Peripheral nerves other than the brachial plexus were affected in 6 patients (23%). In industrialized countries, any neuralgic amyotrophy, particularly if there is bilateral, asymmetric associated with involvement of nerves outside the brachial plexus, should lead physicians to consider a diagnosis of acute hepatitis E.