Dominant PURA variants (encoding purine-rich element-binding protein A) cause a neurodevelopmental disorder with hypotonia, cognitive impairment, and variable neuromuscular symptoms. Clinical presentations and response to pyridostigmine, moreover, highlighted neuromuscular junction (NMJ) involvement. However, NMJ architecture, underlying molecular mechanisms, and potential minimally invasive biomarkers in PURA syndrome remain poorly characterized. This study aimed to profile PURA-related disease using integrated clinical, histological, ultrastructural, transcriptional, and protein analyses of skeletal muscle and blood. Ten genetically confirmed patients underwent detailed phenotyping with emphasis on congenital myasthenic syndrome (CMS)-like features. Quadriceps biopsy from one patient was analyzed by histology, immunohistochemistry, and electron microscopy. Protein profiling of muscle, serum, and extracellular vesicles (EVs) was performed by ELISA and mass spectrometry, with validation by qPCR. In line with the recognized classification of PURA syndrome as a CMS subtype, our patients exhibited hypotonia, ptosis, ocular weakness, and myopathic facies, reflecting impaired neuromuscular transmission. Subtle vesicle accumulation and minor NMJ alterations suggest possible neuromuscular involvement in PURA syndrome. Muscle proteomics showed reduced PURA protein and dysregulation of transcriptional regulation, vesicle transport, extracellular matrix remodeling, and complement activation. qPCR confirmed POSTN and PHGDH upregulation among others. Serum analyses demonstrated elevated TSP4, identifying a promising candidate blood biomarker for PURA-associated NMJ dysfunction. EV proteomics revealed dysregulated immunoglobulins, complement components, and novel candidates including NOTCH2, TARSH, and PON1. Pathogenic PURA variants may impair NMJ structure and vesicle homeostasis, potentially linking molecular and ultrastructural defects with clinical myasthenic features and pyridostigmine responsiveness. Proteomic analysis of skeletal muscle provides initial molecular insights into the consequences of dominant PURA variants in muscle tissue. The identification of TSP4 and extracellular vesicle-associated proteins as potential minimally invasive biomarkers provides a framework for biochemical monitoring of PURA syndrome.

Abstract Involvement of the complement system in myasthenia gravis (MG) depends on the IgG subclass of the mediating antibody. LRP4 antibodies (LRP4-ab) are typically of the IgG1 or IgG2 subclass, implying distinct capacities to activate complement. The extent and pattern of complement involvement in LRP4-ab⁺ MG remain insufficiently characterized at the human neuromuscular junction (NMJ). We examined intercostal muscle biopsies from seven patients with LRP4-ab⁺ generalized MG using immunohistochemistry, immunofluorescence including IgG-subtyping, electron microscopy (EM), and qPCR for complement-associated gene expression. AChR-ab⁺ MG patients and non-disease controls served as comparators. C5b-9 deposition at NMJs was observed in all LRP4-ab⁺ biopsies, affecting 6–96% of identified endplates. Co-localization with IgG1 was consistently detected, whereas IgG2 and IgG4 were absent. One double-seropositive patient showed focal IgG3 staining. Complement transcript levels (C1QC, C3) were higher in LRP4-ab⁺ and AChR-ab⁺ MG compared with controls. Ultrastructural analysis revealed reduced and shortened postsynaptic clefts in 3/4 evaluable LRP4-ab⁺ patients. One therapy-refractory LRP-ab + MG patient with complement deposition and endplate destruction improved after targeted complement inhibition was introduced to his therapeutic regimen, which was based on the biopsy finding. Our findings provide in situ evidence of classical complement pathway activation and associated structural alterations at the human NMJ in LRP4-ab⁺ MG. These tissue-based data contribute to a better understanding of the pathophysiology in this rare MG subgroup.

Chimeric antigen receptor (CAR) T cell-mediated B cell depletion has demonstrated efficacy in several autoimmune diseases. Here we report clinical and molecular data obtained during the nonrandomized phase 1 part of the phase 1/2 COMPARE trial, evaluating safety and efficacy of mivocabtagene autoleucel (miv-cel), an autologous fully human CD19 CAR T cell therapy, in rheumatoid arthritis (RA). Six patients (three men, three women) with severe, treatment-refractory, anti-citrullinated protein antibody (ACPA)-positive RA received a single infusion of miv-cel after stopping all disease-modifying antirheumatic drug treatments and after standard lymphodepletion therapy. Patients were followed for 36-52 weeks for safety and efficacy. Primary endpoints were the incidence and severity of cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS) and adverse events (AEs) within the first 4 weeks after treatment. Secondary and explorative endpoints assessed clinical efficacy and cellular and humoral immune responses. CRS occurred in all patients and was limited to grade 1 and 2 events. No ICANSs or serious AEs occurred; one dose-limiting toxicity was recorded (grade 3 transaminase elevation, resolved without sequelae). The primary endpoint was met with acceptable safety findings, allowing advancement to phase 2. CAR T cell therapy resulted in depletion of CD19+ B cells across blood and tissue, coinciding with a continuous decline of autoantibodies with seroconversion in four of the six patients for ACPAs against mutated citrullinated vimentin and five of six for rheumatoid factor immunoglobulin M. Despite cessation of immunosuppressive treatments, disease activity improved in all patients (median 34% DAS28-CRP reduction at the latest follow-up with DAS28-CRP remission and American College of Rheumatology 70% response in 3 of 6 patients). CD19 CAR T cells showed acceptable short-term tolerability in patients with treatment-refractory RA, justifying further evaluation. ClinicalTrials.gov identifier: NCT06475495 .

Objectives Inclusion body myositis (IBM) is an idiopathic inflammatory myopathy characterised by type 1 inflammation, driven by muscle-infiltrating KLRG1+ and TBX21+ cytotoxic T cells. However, the cellular sources of the stimuli that trigger this effector response in the muscle of patients with IBM remain unclear. Given their role as antigen-presenting cells, we hypothesised that these may be myeloid dendritic cells (mDCs), which have previously been reported in skeletal muscle of patients with IBM. We used immunohistochemistry, immunofluorescence, single-nucleus RNA-sequencing (snRNA-seq) and bulk RNA-sequencing (RNA-seq) data from skeletal muscle of patients with IBM, other myositis, and controls to identify mDCs and characterise their contribution to IBM inflammation. Methods We first analysed snRNA-seq data from 3 datasets to identify, quantify, and characterise 3 mDC subsets: type 1 conventional dendritic (cDC1) cells, type 2 conventional dendritic (cDC2) cells, and mature immunoregulatory dendritic (mregDC) cells. We then analysed RNA-seq data from 2 datasets to correlate specific markers of these subsets with markers of IBM disease activity. We used immunohistochemistry and immunofluorescence to confirm mDC presence. Results All 3 mDC subsets, and especially cDC1 cells, are relatively increased in the muscle of patients with IBM and correlate strongly with IBM-specific inflammatory markers, including KLRG1 and TBX21. In particular, cDC1 cells specifically express the KLRG1 ligands, CDH1 and CDH2, and, along with mregDC cells, IL12B, representing possible juxtacrine and paracrine signals for effector T cells in IBM. Conclusions Skeletal muscle of patients with IBM is specifically characterised by mDC subsets that correlate with markers of cytotoxic T cells and type 1 inflammation.

Abstract Gene therapy is rapidly emerging as a transformative treatment for monogenic neurological disorders, including pediatric movement disorders such as aromatic L-amino acid decarboxylase (AADC) deficiency. However, its success critically depends on defining target cells and windows for therapeutic intervention. Here, we present an open-access single-nucleus transcriptomic atlas of the human basal ganglia spanning a therapy-relevant window from second/third trimester to the perinatal period and adulthood. Across 35,755 nuclei, we identify major (non-)neuronal cell types, retrace developmental trajectories, and characterize generegulatory networks. We identify so far unrecognized human-specific expression of key neuronal signaling genes, including GNAO1 and ADCY5 , and discuss the implications for targeted gene replacement therapies. Unexpectedly, we found that the Huntingtin gene ( HTT ) is already expressed during prenatal stages of human brain development, supporting a previously proposed neurodevelopmental component of Huntington’s disease, which should be considered in diagnostic and therapeutic strategies. Moreover, FOXG1 expression and regulon activity are predominantly located in a prenatal time window, suggesting constraints on the effectiveness of postnatal interventions. Our findings highlight the importance of datasets capturing human brain development in real time and provide a publicly available resource to guide precision gene therapy strategies in the future. Graphical abstract

Brachio-cervical inflammatory myopathy (BCIM) is a rare and under-characterized subtype of idiopathic inflammatory myopathies (IIM), marked by prominent upper limb and neck muscle involvement. Since its initial description in 2006, few studies have addressed its clinical spectrum or pathogenesis, and its potential overlap with systemic sclerosis (SSc) remains a matter of debate. Here, we aimed to characterize the clinical, histopathological, and molecular features of BCIM in a large multicenter cohort and determine whether BCIM represents a characteristic clinico-pathological syndrome within the IIM spectrum or reflects an atypical presentation of SSc-associated myositis. We studied 26 patients with clinically and histologically confirmed BCIM from seven European centers. Clinical data, treatment responses, and autoantibody profiles were collected retrospectively from participating centers. Histopathological and immunohistochemical analyses were performed on muscle biopsies, and 12 muscle biopsy specimens underwent bulk RNA sequencing, including a comparison with 669 non-BCIM myositis datasets. Proteomic profiling was performed in an independent subset. Clinical overlap with SSc was defined using the 2013 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria. The cohort was predominantly female (88

During muscle contraction, increased influx of calcium from the myocyte cytosol into the mitochondrial matrix through the mitochondrial calcium uniporter (MCU) links calcium homeostasis with high ATP provision. The MCU is located at the inner mitochondrial membrane and one of its structural components, the mitochondrial calcium uniporter regulator 1 (MCUR1), promotes its activity. Although MCUR1 function has been studied in cell models, mutations have not yet been associated with human disease. Here, we present a patient with proximal muscle weakness and atrophy, showing histological features of autophagic vacuoles with sarcolemmal features, who carries a homozygous MCUR1 nonsense mutation. To investigate the underlying mechanisms of muscle pathology, we examined patient fibroblasts and quadriceps muscle specimens. MCUR1 deficiency compromised mtCa2+ uptake, that had been stimulated both by histamine or rising extracellular calcium exposure. Autophagic flux and histologic markers for autophagy (LAMP2, LCB3) were increased in the patient. However, the MCUR1 mutation did not alter MCU-complex assembly or its subcellular location, nor the resting mitochondrial membrane potential. Our study associates MCUR1 deficiency with mitochondrial dysfunction and autophagic vacuolar myopathy, thereby highlighting the crucial role of mtCa2+ uptake in regulating mitochondrial function and expanding the spectrum of mitochondrial disorders in humans.

OBJECTIVES:Granulomatous myositis (GM) is defined by focal collections of activated macrophages that fuse to form multinucleated cells that aggregate into granulomas within skeletal muscle. This study aimed to elucidate the pathophysiology of GM by defining its specific transcriptomic profile. METHODS:Bulk RNA sequencing was performed on 722 muscle biopsies, including 38 from patients with GM, other myopathies and healthy comparators. Spatial transcriptomics and immunohistochemistry assays were used to identify the location of specific transcripts and proteins within the tissue. RESULTS:We conducted a systematic analysis of the inflammatory pathways implicated in GM. This analysis revealed that GM muscle biopsies are characterized by elevated levels of IFNγ, IFNγ-inducible genes and proinflammatory cytokine genes including IL1B, TNF and TGFB1. Additionally, we identified a specific gene signature in GM, comprising 1293 genes that were significantly upregulated and 256 significantly downregulated. These genes were strongly correlated with transcriptomic markers of disease activity. Using this gene signature, support vector machine models accurately identified GM, achieving an area under the curve of 99.6% (99.0-99.9%) and an accuracy of 98.6% (98.2-98.9%). Among the identified genes, CHIT1 emerged as the most significantly upregulated gene, with its expression strongly correlating with disease severity. Furthermore, CHIT1 was detected at both the RNA and protein levels in granulomas and giant cells. CONCLUSION:GM is transcriptomically characterized by a strong IFNγ signature and overexpression of proinflammatory cytokines, including IL1B, TNF and TGFB1. Additionally, it exhibits a unique transcriptomic profile, including CHIT1, which correlates with disease activity.

Muscle biopsy (MB) is an important tool to help differentiate idiopathic inflammatory myopathies (IIMs) from hereditary muscular diseases (HMDs). The usefulness of immunohistochemical stains of the major histocompatibility complex class I and the membrane attack complex are controversial, as both may be identified in some HMDs. More sensitive markers of IIMs have recently been used, such as myxovirus resistance A (MxA), a type I interferon-inducible protein. We selected skeletal MB samples from 81 patients diagnosed with IIM and HMD harbouring overt inflammatory infiltrates on their MBs in the period between March 2022 and September 2024. Two groups were identified: the IIM group (46 cases) and the HMD group (35 cases). We characterized and compared the patterns of MxA protein expression among the two groups. In the IIM group, positive sarcoplasmic MxA expression was detected on the myofibres of 10 patients (24%), among whom were eight dermatomyositis patients. In the HMD group, we did not identify any sarcoplasmic positivity. However, five patients (14%) showed positive labelling restricted to the sarcolemmal membrane, including non-necrotic or regenerating fibres. Our study demonstrates the value of MxA for increasing dermatomyositis diagnostic accuracy and suggests the potential role of interferon type I in the pathophysiology of HMD.

Idiopathic inflammatory myopathies (IIMs) are autoimmune muscle diseases with distinct clinical, histopathological, and molecular features. Among them, inclusion body myositis (IBM) is refractory to immunotherapy and characterized by combined inflammatory and degenerative changes. Polymyositis with mitochondrial pathology (PM-Mito) has been proposed as a prodromal stage of IBM, but molecular profile underlying this spectrum remains poorly defined. Skeletal muscle biopsies from 38 IBM, 14 PM-Mito, 5 anti-synthetase syndrome (ASyS), 3 dermatomyositis (DM), 5 immune-mediated necrotizing myopathy (IMNM), and 7 non-diseased controls (NDC) were analyzed by label-free mass spectrometry and validated by bulk RNA sequencing. Dimensionality reduction was performed using sparse Partial Least Squares Discriminant Analysis (sPLS-DA), followed by differential protein analysis. IBM exhibited a homogeneous and distinct proteomic signature compared with other IIM subtypes, driven by upregulation of MHC class I (e.g. HLA-A) and II (e.g. HLA-DRB1, CD74) molecules, and cytoskeletal proteins (e.g. PDCL3). Comparing IBM to other types of IIM, we also detected increased level of specific histone variants (e.g. HIST2H2AA3, H1FX). Enrichment analysis of the differential proteins underscored increased antigen presentation and T-cell–mediated immunity pathways, with concomitant depletion of mitochondrial respiratory chain, RNA processing, and oxidative phosphorylation components in IBM. PM-Mito shared a proteomic profile with IBM with reduced MT-ND2 levels and increases in lipid storage regulator PLIN1 and extracellular matrix protein COL14A1, among others. In contrast to IBM, PM-Mito preserved type 2 myofiber markers (e.g. MYH2). A specific protein change to PM-Mito was an increase in the cytochrome c oxidase subunit III (MT-CO3), implicating mitochondrial remodelling. Transcriptomic analysis validated the proteomic changes in COL14A1, IGLL4, PLIN1, MT-ND2, SMDT1, and TIMM21, all of which were shared between IBM and PM-Mito. IBM exhibits a unique proteomic landscape distinct from other IIMs. The overlap with PM-Mito suggests that these conditions share molecular features, supporting an interpretation that places PM-Mito in the broader spectrum of IBM. Novel protein markers, including histone variants and cytoskeletal regulators, highlight potential pathways for future research. These findings underscore the need for longitudinal studies exploring therapeutic targets in early disease stages.

Immune-mediated necrotizing myopathy (IMNM) associated with antibodies against 3‑hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) is typically a severe autoimmune myopathy requiring immunosuppressive therapy. Rare spontaneous remissions after discontinuation of statins have been reported, suggesting that the disease course may be more heterogeneous than previously assumed. We retrospectively identified four patients with anti-HMGCR-positive IMNM who experienced full recovery without immunosuppressive treatment. All had developed proximal muscle weakness and markedly elevated creatine kinase levels (8-80 times the upper limit of normal) during statin therapy, and they fulfilled the histopathological criteria of IMNM, except for the p62-pattern. After statin withdrawal, all patients recovered within 6-12 months without specific treatment. Two later relapsed after statin re-exposure and again improved after statin discontinuation. One patient relapsed after a flu-like illness. During long-term follow-up of up to ten years, three patients remained asymptomatic, two despite persistently elevated antibody titers, and one patient was started on intravenous immunoglobulins. These findings indicate that a subset of anti-HMGCR IMNM may follow a self-limited or relapsing-remitting course. While these cases broaden the clinical spectrum of anti-HMGCR IMNM, their implications for management remain uncertain and warrant further investigation.

OBJECTIVES:Autoantibody internalisation has been implicated in autoimmune disease pathogenesis, yet its mechanisms and generalisability across diseases, cell types, and tissues remain poorly defined. We sought to address these gaps. METHODS:Bulk RNA sequencing was performed on 814 muscle biopsies from patients with autoimmune diseases and healthy controls, including an external validation cohort of 41 additional samples. Purified patient immunoglobulin (Ig) G was electroporated into primary human cells to assess functional effects in vitro. Immunofluorescence evaluated localisation of immunoglobulins across diseases and tissues. Spatial transcriptomics assessed disease-specific gene expression, cellular injury, and inflammatory responses. RESULTS:Using anti-Mi2 dermatomyositis and anti-PM/Scl scleromyositis as model diseases, we validated reproducible, autoantibody-specific transcriptomic signatures consistent with autoantigen dysfunction across cohorts and confirmed that electroporation of purified patient IgG into healthy primary cells recapitulates these disease-associated transcriptional programmes. Spatial transcriptomics linked these signatures to cellular injury and distinct inflammatory responses, including activation of type I interferon and TGFβ signalling in anti-Mi2 dermatomyositis and type II interferon signalling in anti-PM/Scl scleromyositis. These programmes were observed predominantly not only in muscle fibres but also in macrophages, endothelial cells, and fibroblasts/fibroadipogenic progenitors. Spatial transcriptomics further revealed transfer of immunoglobulin RNA from antibody-secreting cells to adjacent target cells expressing disease-specific transcriptional programmes. Antibody internalisation, previously described in myositis muscle, was also observed in skin from patients with anti-Mi2 and anti-PM/Scl and in tissues from anti-U1RNP mixed connective tissue disease, anti-Ku overlap syndrome, and anti-Scl70 systemic sclerosis. CONCLUSIONS:Together, these findings establish autoantibody internalisation as a mechanism of tissue injury in autoimmunity, suggesting its broader relevance across autoantibody-mediated diseases.

Abstract Idiopathic inflammatory myopathies (IIMs) are autoimmune disorders defined by persistent muscle inflammation, fibrosis, and frequent resistance to current therapies. However, the mechanisms perpetuating disease activity despite immunosuppressive treatment remain elusive. Here, we describe a novel role for tissue-resident stromal cells, specifically fibro-adipogenic progenitors (FAPs), in sustaining skeletal muscle inflammation. Utilizing single-nucleus and spatial transcriptomics in 24 IIM patients and six non-diseased controls, we describe how FAPs adapt to their tissue context, favoring T-cell–centric programs in T-cell environments and myeloid programs in macrophage environments. At the spatial level, FAPs form inflammatory niches by co-localizing with muscle stem cells and activated macrophages, positioning them to participate in cell-to-cell communication with both immune and muscle cells. Trajectory and ligand-receptor analyses suggest a dual-input mechanism whereby infiltrating immune cells (via TGF-β) and myofibers (via epidermal growth factor (EGF)) converge on the AP-1 transcription factor to drive FAP differentiation toward a pro-inflammatory and pro-fibrotic phenotype. Mechanistically, exposure of primary human FAPs to TGF-β and EGF induces a primed state by altering the accessibility to AP-1 regulatory elements. Together, our findings reveal a previously unrecognized role of tissue-resident stromal cells in IIM, highlighting microenvironmental cross-talk centered on FAPs as a promising and actionable therapeutic target.

Data on chronic autoimmune neuropathies (CAN) requiring intensive care unit (ICU) treatment are limited. This study investigated clinical and neuropathological features, immunotherapies, and outcomes of ICU-treated CAN patients. Retrospectively, we analyzed patients with CAN admitted to the ICU between 2007 and 2024. Outcomes, assessed by Inflammatory Neuropathy Cause and Treatment (INCAT) score and modified Rankin scale (mRS), were compared to age, sex, and diagnosis-matched non-ICU outpatients using ordinal and binary logistic regression. Among 21 included patients (chronic inflammatory demyelinating neuropathies (CIDP): n = 15, other CAN: n = 6), 95

Severe neuropathies with predominant involvement of motor fibres can resemble lower motor neuron disease (LMND) phenotypes. Given the fatal prognosis of LMND, identifying underlying autoimmune syndromes is crucial to provide treatment options to patients. We investigated a novel autoantibody binding pattern observed on murine teased sciatic nerve fibres. Target antigens were identified using immunoprecipitation combined with mass spectrometry. Target specificity of these autoantibodies was validated in cell-based assays, neutralization assays and knock-out models. A retrospective study cohort consisting of different neuropathies (chronic inflammatory demyelinating polyradiculopathy n = 86, Guillain-Barré syndrome n = 37, multifocal motor neuropathy n = 18, diabetic neuropathy n = 30, other inflammatory neuropathies n = 10), amyotrophic lateral sclerosis (n = 50), multiple sclerosis (n = 50) and healthy controls (n = 50) was negative for septin multimer autoantibodies. Histopathological analysis of skin and the sural nerve including electron microscopy was performed in one seropositive patient, and autoantibody binding was characterized in vitro. Extensive immunotherapy was initiated in one patient, with clinical and serological follow-up over 4 years. Among 3543 total samples tested, three patients (two male, one female)-diagnosed with the LMND variant of amyotrophic lateral sclerosis (aged 65, 72 and 79 years, respectively)-showed a novel and distinct autoantibody binding pattern of indirect immunofluorescence staining on peripheral nerves, targeting Schmidt-Lanterman incisures (SLIs), paranodes and the abaxonal myelin. Target identification and validation revealed septin multimers as autoantibody epitopes. Despite the primarily intracellular location of septins, autoantibody binding was evident in living myelinated dorsal root ganglia, primarily at SLIs ('incisuropathy'). Septin multimer autoantibodies further initiated complement deposition on fixed and permeabilized cell-based assays. Sural nerve and skin biopsies showed inflammation, myelin and axonal pathology. Extensive immunotherapy in one patient was followed by disease stabilization over 3 years. The other two patients died of rapid disease progression: one of them received no immunotherapy while the other had ineffective treatments with single administrations of intravenous immunoglobulin and rituximab. Our data suggest that septin multimer autoimmunity occurs in severe motor-predominant neuropathies which can clinically resemble a neurodegenerative LMND. Screening for septin multimer autoantibodies should be considered in patients presenting with this phenotype. Follow-up studies need to determine the direct pathogenicity of septin multimer autoantibodies, their potential as a biomarker of an autoimmune syndrome and responses to immunotherapy in larger cohorts.

We report the case of a 54-year-old male patient with Behçet Disease (BD) complicated by aseptic pyomyositis with features of medium vessel vasculitis. His clinical course was characterized by severe myalgia, a palpable mass in the left quadriceps, blistering and ulcerative skin lesions, and systemic inflammation. Laboratory tests revealed neutrophilic leukocytosis, markedly elevated C-reactive protein, and approximately 13-fold increased creatine kinase levels. MRI demonstrated diffuse and asymmetric skeletal muscle oedema in the lower limbs, suggestive of multifocal abscess-like lesions. Muscle biopsy revealed sterile pyomyositis with granulocytic-necrotizing infiltrates and fibrinoid vascular necrosis with massive endomysial inflammatory infiltration. Muscle symptoms responded well to high-dose corticosteroid therapy, while cutaneous ulcers were initially refractory and improved only after multiple immunosuppressive treatments. This case highlights the complexity of diagnosing and managing severe muscular involvement and treatment-resistant skin manifestations in the context of BD.

The pathomechanism of sarcoid polyneuropathy remains unknown though different hypotheses are discussed. A 57-year-old female patient presented with painful paresthesia and progressive weakness of the lower extremities. Intravenous immune globulin therapy for presumed chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) failed to control disease activity. Glucocorticoid pulse therapy was associated with rapid improvement of the neurological symptoms and resolved the conduction block, which indicates inflammatory processes involved in sarcoid polyneuropathy pathogenesis.