IgG4 and IgE co-positive group found in idiopathic orbital inflammatory disease

AIM： To reveal the cytokines involved in idiopathic orbital inflammatory disease（IOID） and the relationship between Th17 cells, IgE and IOID pathogenesis.METHODS： Whole blood samples were processed immediately after collection and serological IgG4, IgG, and IgE antibodies were tested using ELISA. IOID and orbital cavernous hemangioma（CH） tissue samples underwent Bio-Plex multiplex cytokine detection. Hematoxylin-Eosin（HE） staining of all paraffin samples suggested the histological features of IOIDs, and expressions of IgG4 and IL-17 A in affected tissues were detected by immunohistochemistry. RESULTS： Among 40 IOID plasma samples, 52.5%（21/40） were positive for IgG4 and 25%（10/40） were positive for IgE. Overlapped IgG4 or IgE positive samples accounted for 22.5%（9/40）. Therefore, IOID samples were separated into three groups. The IgE＋/IgG4＋ group had a relevantly lower level of pro-inflammatory cytokine expression. IL-4（Th2 cell related）, IL-10 and TGF-β1（Treg cell immunity related） were elevated in all three groups. Some of the Th17 cell related cytokines（i.e. IL-17 A/F, IL-25, IL-23, and IL-33） displayed higher expression levels in the IgE-/IgG4-group compared to the other two groups.CONCLUSION： We discovered an IgG4-IgE co-positive group as well as Th17 cell immune involvement in IgG4-IgE co-negative subgtroup in IOID for the first time. The pathogenesis of IOID could differ from different subgroups according to the IgG4 and IgE detection. Therefore, we recommend that, Treatment stratagy should be made according to the clinical assessment of IgG4-IgE and Th17 profile detection.

Epstein-Barr virus-encoded small RNAs in idiopathic orbital inflammatory pseudotumor tissues: a comparative case series

AIM： To investigate the positive rate and types of cells that express Epstein-Barr virus-encoded small RNAs （EBERs） and to determine the distribution of EBER-expressing cells in idiopathic orbital inflammatory pseudotumor （IOIP） tissues. METHODS： We retrospectively examined 40 archived paraffin specimens from two teaching hospitals in Southern China between January 2007 and January 2015 that were pathologically determined to exhibit IOIP. Eleven concurrent paraffin specimens of thyroid-associated ophthalmopathy （TAO） composed the control group. In situ hybridization was performed to detect EBERs. Immunohistochemistry was employed to detect CD3, CD20, Vimentin, and smooth muscle actin （SMA）, and the positive rate, types of positive cells, and distribution and location of EBERs were evaluated. RESULTS： The positive expression rate of EBERs was 47.5% （19/40） in the IOIP group, which was significantly higher than that in the TAO group [0 （0/11）, P=-0.011]. in the IOIP group, the lymphocyte infiltrative subtype, fibrotic subtype, and mixed subtype exhibited EBER-positive rates of 57.1% （12121）, 12.5% （118）, and 54.5% （6/11）, respectively, and no significant differences were found between these subtypes （P=0.085）. Positive signals of EBERs were mainly present in medium-small lymphocytes between or around follicles and in the nuclei of activated immunoblasts （14/19）. CONCLUSION： The positive rate, types, and distribution of EBER-expressing cells in IOIP have been documented.These findings are conducive for a better understanding of the underlying mechanisms of Epstein-Barr virus infection in IOIP pathogenesis.

Idiopathic inflammatory demyelinating diseases of the central nervous system in patients following allogeneic hematopoietic stem cell transplantation： a retrospective analysis of incidence, risk factors and survival

Background AIIogeneic hematopoietic stem cell transplantation （allo-HSCT） is a curative therapy for many hematological diseases, but there are many complications following alIo-HSCT, among which neurological complications （NC） are one of the most commonly described ones. However, little is known about idiopathic inflammatory demyelinating diseases （IIDDs） of the central nervous system （CNS） in patients following alIo-HSCT. Methods A nested case-control study was conducted in a large cohort of 1365 patients, who underwent alIo-HSCT at the Institute of Hematology and Peking University People＇s Hospital, between January 2004 and December 2009, 36 patients of whom developed CNS IIDDs. Kaplan-Meier method, univariate and multivariate Cox regression were applied in our statistical analysis using SPSS 16.0. Results The cumulative incidence of all cases of IIDDs at 6 years posttransplantation was 3.6%. Thirty-five patients （97.2%） suffered IIDDs after transplantation, 16 patients （44.4%） between day 0 to day 100 post-transplantation, 10 patients （27.8%） between day 100 to 1 year post-transplantation, and 9 patients （25.0%） 1 year post-transplantation. Multivariate regression analysis identified donor type （P=0.031）, infection （P=0.009）, and acute lymphatic leukemia （P=0.017） as independent risk factors for posttransplantation IIDDs. The median survival time of patients with IIDDs was 514 days after transplantation （95% CI： 223-805）. Survival at 6 years was significantly lower in patients who developed the diseases compared to those who did not （26.6% vs. 73.5%, P 〈0.001）. Of the 36 patients experiencing IIDDs, 58.3% （n=21） died. The causes of death were graft-versus-host disease （GVHD） （n=4）, underlying disease relapse （n=3）, infections （n=12）, and other causes （n=2）. Conclusions IIDDs is an uncommon but serious complication of alIo-HSCT, especially in patients with a primary diagnosis of acute lymphatic leukemia, mismatched transplants, and infections. Our study results indicate that patients with IIDDs tend toward a poor prognosis following alIo-HSCT.

Neurological manifestations related to Crohn’s disease:a boon for the workforce

The neurological manifestations of Crohn’s disease and its prevalence are not well known.Here,we report five patients of confirmed Crohn’s disease with different neurological presentations.The neurological presentations include anterior ischemic optic neuropathy,myelopathy,posterior reversible encephalopathy syndrome,chronic inflammatory demyelinating polyneuropathy,and chronic axonal sensory and motor polyneuropathy.These manifestations should be kept in mind in the assessment of Crohn’s disease.