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Systemic sclerosis (SSc) is a disease at the intersection of autoimmunity and fibrosis. However, the epigenetic regulation and the contributions of diverse cell types to SSc remain unclear. Here we survey, using ATAC-seq, the active DNA regulatory elements of eight types of primary cells in normal skin from healthy controls, as well as clinically affected and unaffected skin from SSc patients. We find that accessible DNA elements in skin-resident dendritic cells (DCs) exhibit the highest enrichment of SSc-associated single-nucleotide polymorphisms (SNPs) and predict the degrees of skin fibrosis in patients. DCs also have the greatest disease-associated changes in chromatin accessibility and the strongest alteration of cell–cell interactions in SSc lesions. Lastly, data from an independent cohort of patients with SSc confirm a significant increase of DCs in lesioned skin. Thus, the DCs epigenome links inherited susceptibility and clinically apparent fibrosis in SSc skin, and can be an important driver of SSc pathogenesis., Systemic sclerosis (SSc) is a disease with manifestation in the skin and immune etiology, but the pathogenic immune cell types remain unidentified. Here the authors use ATAC-seq to profile chromatin landscapes of skin samples from patients with SSc to implicate skin dendritic cells for having the strongest disease-associated epigenetic changes.

From response to vaccinations to autoimmune disease, gender differences in immunity have been long recognized in clinical medicine. The primary genetic difference between males and females is the complement of sex chromosomes. The X chromosome contains a far higher number of genes than the Y chromosome, and it has long been thought that the second X in females was effectively silenced to provide genetic equity or dosage compensation. Emerging technologies are telling an increasingly fascinating story and calling to question long held assumptions about the silenced X chromosome, suggesting that the X may be a regulator of immune system function in health and disease. It has been long postulated that epigenetic or regulatory differences between male and female immune cells may underlie immune difference and autoimmune susceptibility and emerging science suggests that sex-chromosome and autosomal gene regulation may contribute to immune variation and provide insight into gender differences in health and disease. Herein we review recent findings on gender differences in immunity, with a focus on gene regulation and T cells.

Cutaneous small vessel vasculitis (CSVV) is a nonspecific finding with an extensive differential diagnosis. It is critically important to distinguish skin-limited presentations of CSVV from severe life-threatening systemic vasculitides presenting with CSVV as an initial manifestation. It can be challenging to determine which patients presenting with CSVV are at risk for systemic disease. Standard histopathologic evaluation, direct immunofluorescence, and serologic evaluation is typically required to exclude a systemic vasculitis. Type 1 cryoglobulinemia may rarely present with CSVV. Herein, we report a case of type 1 cryoglobulinemia in the setting of occult multiple myeloma. CSVV with prominent intravascular crystal formation was noted. The presence of intravascular crystals in the setting of CSVV may represent an important early clue to the diagnosis of type 1 cryoglobulinemic vasculitis.

Background: Nerve involvement developed in a patient with granuloma annulare, as evidenced by a perineural infiltrate of histiocytes in the dermis. The histopathologic pattern was suggestive of leprosy. No mycobacteria were observed, and neurologic testing was normal. Objective: To determine whether inflammation of the nerves or perineural tissue is common in granuloma annulare, we studied the cutaneous nerves in skin biopsy specimens from 14 patients with granuloma annulare. Methods: Sections were stained with hematoxylin-eosin to highlight inflammatory cells and with S-100 to identify cutaneous nerves. Results: No inflammation around nerves was found in 12 specimens, abutting granulomatous inflammation was found in 1 specimen, and enveloping granulomatous inflammation was found in 1 specimen. No nerves were infiltrated by inflammatory cells. Conclusion: Perineural granulomatous inflammation resembling the perineural infiltrate of leprosy appears to be an uncommon characteristic of granuloma annulare. Clinical correlation and acid-fast stains can assist in establishing the correct diagnosis. Contexte: Une atteinte nerveuse est apparue chez un patient atteint de granulome annulaire, comme en témoignait un infiltrat périneural d'histiocytes dans le derme. Les signes histopathologiques étaient évocateurs de la lèpre, mais aucune mycobactérie n'a été observée, et l'examen neurologique était normal. Objectif: L'étude visait à déterminer si l'inflammation des nerfs ou du tissu périneural est fréquente dans le granulome annulaire; pour ce faire, nous avons examiné les nerfs cutanés dans des prélèvements biopsiques de la peau, effectués sur 14 patients atteints de granulome annulaire. Méthodes: Les coupes ont été colorées à l'hématoxyline-éosine pour mettre en évidence des cellules inflammatoires, ainsi qu'au S-100 pour repérer les nerfs cutanés. Résultats: Aucune inflammation autour des nerfs n'a été observée sur 12 prélèvements, mais il y avait présence d'inflammation granulomateuse contiguë sur un prélèvement et d'inflammation granulomateuse enveloppante, sur un autre prélèvement. Les nerfs n'ont pas été infiltrés par les cellules inflammatoires. Conclusion: L'inflammation granulomateuse périneurale qui ressemble à l'infiltration périneurale observée dans la lèpre semble un signe peu fréquent du granulome annulaire. L'établissement de corrélations cliniques et des colorations résistantes à l'acide peuvent faciliter la pose du bon diagnostic.

The Centers for Disease Control and Prevention's (CDC) Category C consists of biological agents not presently considered public health threats in terms of bioterrorism but which could emerge in this capacity as the scientific understanding of them grows in the future. Category C agents include Nipah virus, the hantaviruses, and multiple drug-resistant (MDR) Mycobacterium tuberculosis. Each is discussed, with special attention paid to weapons application. Keywords: biological weapons; Category C agents; CDC; Centers for Disease Control and Prevention; hantaviruses; HFRS; HPS; multiple drug-resistant Mycobacterium tuberculosis; natural host; Nipah virus; pathogenesis; tuberculosis

A 9-year-old girl presented with a choroidal tumor 6 years after remission of Burkitt lymphoma with no evidence of systemic recurrence. The tumor regressed after plaque radiotherapy. The second tumor could have been related to previous chemotherapy, caused by Epstein-Barr virus infection, or the result of independent lymphoma cell growth.