Azathioprine therapy selectively ablates human Vδ2+ T cells in Crohn’s disease

Tumor-derived and bacterial phosphoantigens are recognized by unconventional lymphocytes that express a Vγ9Vδ2 T cell receptor (Vδ2 T cells) and mediate host protection against microbial infections and malignancies. Vδ2 T cells are absent in rodents but readily populate the human intestine, where their function is largely unknown. Here, we assessed Vδ2 T cell phenotype and function by flow cytometry in blood and intestinal tissue from Crohn’s disease patients (CD patients) and healthy controls. Blood from CD patients included an increased percentage of gut-tropic integrin β7–expressing Vδ2 T cells, while “Th1-committed” CD27-expressing Vδ2 T cells were selectively depleted. A corresponding population of CD27⁺ Vδ2 T cells was present in mucosal biopsies from CD patients and produced elevated levels of TNFα compared with controls. In colonic mucosa from CD patients, Vδ2 T cell production of TNFα was reduced by pharmacological blockade of retinoic acid receptor-α (RARα) signaling, indicating that dietary vitamin metabolites can influence Vδ2 T cell function in inflamed intestine. Vδ2 T cells were ablated in blood and tissue from CD patients receiving azathioprine (AZA) therapy, and posttreatment Vδ2 T cell recovery correlated with time since drug withdrawal and inversely correlated with patient age. These results indicate that human Vδ2 T cells exert proinflammatory effects in CD that are modified by dietary vitamin metabolites and ablated by AZA therapy, which may help resolve intestinal inflammation but could increase malignancy risk by impairing systemic tumor surveillance.     

Anterior interosseous nerve lession and distal myoclonus revealing a parsonage turner syndrome associated with hashimoto thyroiditys

Parsonage-Turner Syndrome (PTS), also known as brachial neuritis or neuralgic amyotrophy, is a rare disorder affecting 2 to 3 individuals per 100,000 each year. Abrupt onset shoulder pain, followed by motor weakness, paresthesia and hypoesthesia, is usually reported, lasting several months with variable recovery. The etiology of the disease may be idiopathic or triggered by an underlying autoimmune disease in genetically susceptible individuals. Our report addresses a unique case of Parsonage-Turner Syndrome in a patient suffering from concurrent Hashimoto Thyroiditis. A previously healthy A 22 year-old female was referred to the Department of Neurology after complaints of sudden-onset motor weakness in her left upper limb. On physical examination, the patient could not make an “Ok sign” with her thumb and distal phalanx or form a complete fist, revealing weakness within the anterior interosseous branch of the median nerve. Further testing with electromyography demonstrated muscular atrophy within the arm''s anterior compartment, forearm, and triceps brachii of the posterior compartment. Additional imaging and physical examination were unremarkable, confirming our diagnosis of PTS. Furthermore, lab reports revealed elevated levels of anti-thyroglobulin and anti-thyroid peroxidase antibodies and our patient was concurrently diagnosed with Hashimoto''s thyroiditis.This case aims to highlight the rare co-occurrence of Hashimoto''s thyroiditis with Parsonage-Turner Syndrome in an otherwise healthy patient. A 2014 study published by Nugent et al. had also shed light on brachial neuritis in a patient suffering from autoimmune connective tissue disease, and through this case study, we hope to add to the growing literature regarding the correlation between PTS and autoimmune diseases. Symptoms of PTS can easily be misdiagnosed given its similarity to other peripheral neuropathies, and careful assessment and thorough understanding of the disease is required to successfully distinguish it from other neurological pathologies.