Chronic Inflammatory Demyelinating Polyneuropathy after ChAdOx1 nCoV-19 Vaccination

Recently several patients, who developed Guillain–Barré syndrome characterized by prominent bifacial weakness after ChAdOx1 nCoV-19 vaccination, were described from different centers. We recently observed a patient who developed a similar syndrome, later in the follow up he showed worsening of the neuropathy two months after the initial presentation. Repeat EMG showed reduced nerve sensory and motor conduction velocities of both upper and lower limbs, and a diagnosis of chronic inflammatory demyelinating polyneuropathy (typical CIDP) was made according to established criteria. Our report expands on the possible outcomes in patients who develop Guillain–Barrè syndrome after COVID-19 vaccinations and suggest that close monitoring after the acute phase is needed in these patients to exclude a chronic evolution of the disease, which has important implications for long-term treatment

Familial autoimmune MuSK positive myasthenia gravis

The familial occurrence of autoimmune myasthenia gravis (MG) with anti-acetylcholine receptor antibodies (AChR Ab) has been rarely reported. Different antibody specificity in family members has also been described. To our knowledge, a familial form of MuSK Ab positive MG has never been reported. We studied the HLA allele profile in a family with two sisters affected by MuSK positive MG

Quantification of circulating alpha-1-antitrypsin polymers associated with different SERPINA1 genotypes

Objectives: Alpha-1-antitrypsin deficiency is a genetic disorder caused by mutations in the SERPINA1 gene encoding alpha-1-antitrypsin (AAT), the major serine protease inhibitor in plasma. Reduced AAT levels are associated with elevated risk of developing emphysema mainly due to uncontrolled activity of neutrophil elastase in the lungs. The prevalent Z-AAT mutant and many rare pathogenic AAT variants also predispose to liver disease due to their accumulation as polymeric chains in hepatocytes. Part of these polymers are secreted into the bloodstream and could represent biomarkers of intra-hepatic accumulation. Moreover, being inactive, they further lower lung protection against proteases. Aim of our study is to accurately quantify the percentage of circulating polymers (CP) in a cohort of subjects with different SERPINA1 genotypes. Methods: CP concentration was measured in plasma or Dried Blood Spot (DBS) by a sensitive sandwich ELISA based on capture by the polymer-specific 2C1 monoclonal antibody. Results: CP were significantly elevated in patients with the prevalent PI*SZ and PI*ZZ genotypes, with considerable intra-genotype variability. Notably, higher percentage of polymers was observed in association with elevated C-reactive protein. CP levels were also increased in carriers of the Mmalton variant, and of Mprocida, I, Plowell and Mherleen in heterozygosity with Z-AAT. Conclusions: These findings highlight the importance of implementing CP quantification in a clinical laboratory. Indeed, the variable amount of CP in patients with the same genotype may correlate with the variable severity of the associated lung and liver diseases. Moreover, CP can reveal the polymerogenic potential of newly discovered ultrarare AAT variants

HERV-K Modulates the Immune Response in ALS Patients

Human endogenous retrovirus (HERV)-K env-su glycoprotein has been documented in amyotrophic lateral sclerosis (ALS), where HERV-K env-su 19–37 antibody levels significantly correlated with clinical measures of disease severity. Herein, we investigated further the humoral and cell-mediated immune response against specific antigenic peptides derived from HERV-K in ALS. HERV-K env glycoprotein expression on peripheral blood mononuclear cells (PBMCs) membrane and cytokines and chemokines after stimulation with HERV-K env 19–37 and HERV-K env 109–126 were quantified in patients and healthy controls (HCs). HERV-K env glycoprotein was more expressed in B cells and NK cells of ALS patients compared to HCs, whereas HERV-K env transcripts were similar in ALS and HCs. In ALS patients, specific stimulation with HERV-K env 109–126 peptide showed a higher expression of IL-6 by CD19/B cells. Both peptides, however, were able to induce a great production of IFN-γ by stimulation CD19/B cells, and yielded a higher expression of MIP-1α and a lower expression of MCP-1. HERV-K env 19–37 peptide induced a great production of TNF-α in CD8/T cells. In conclusion, we observed the ability of HERV-K to modulate the immune system, generating mediators mainly involved in proinflammatory response