Clinical and molecular features of X-linked hyper IgM syndrome – An experience from North India

Publication date: Available online 25 July 2018

Source: Clinical Immunology

Author(s): Amit Rawat, Babu Mathew, Vignesh Pandiarajan, Ankur Jindal, Madhubala Sharma, Deepti Suri, Anju Gupta, Shubham Goel, Adil Karim, Biman Saikia, Ranjana W. Minz, Kohsuke Imai, Shigeaki Nonoyama, Osamu Ohara, Silvia Clara Giliani, Luigi D. Notarangelo, Koon-Wing Chan, Yu-Lung Lau, Surjit Singh

Abstract

X-linked hyper IgM Syndrome (XLHIGM), the most frequent form of the Hyper IgM syndromes is a primary immune deficiency resulting from a mutation in the CD40 ligand gene (CD40LG). We analyzed the clinical and laboratory features of ten patients with XLHIGM, who were diagnosed at a tertiary care hospital in North India. Most common infections were sinopulmonary infections (80%) and diarrhea (50%). Sclerosing cholangitis and necrotising fasciitis were noted in one patient each. Three novel mutations in CD40LG (c.429_429 delA, p. G144DfsX5; c.500 G > A, p.G167E and c.156 G > C, p.K52 N) were detected. In addition, we found one missense mutation, two splice site mutations and two large deletions, which have been previously reported. Four (4) patients had expired at the time of analysis. We report the first series of XLHIGM from North India where we have documented unique features such as pulmonary alveolar proteinosis and infections with Mycobacterium sp.

https://ift.tt/2v46vaG

Allergic Contact Dermatitis To Personal Care Products And Topical Medications In Adults With Atopic Dermatitis

Publication date: Available online 25 July 2018

Source: Journal of the American Academy of Dermatology

Author(s): Supriya Rastogi, Kevin R. Patel, Vivek Singam, Jonathan I. Silverberg

ABSTRACT

Background

Atopic dermatitis (AD) is associated with skin-barrier disruption, immune dysregulation, and application of emollients and topical medications, which may predispose towards developing allergic contact dermatitis (ACD).

Objective(s)

To determine the predictors of ACD and relevant allergens in AD.

Methods

A retrospective chart review was performed of 502 adults (age ≥18 years) who were patch-tested to an expanded allergen series from 2014-2017.

Results

Overall, 108 (21.5%) had current AD and 109 (21.7%) had past AD. Patients with vs. without current AD had similar proportions of any positive (+/++/+++: 80 [74.1%] vs. 254 [64.5%]; Chi-square, P=0.06), stronger (++/+++: 34 [31.5%] vs. 102 [25.9%], P=0.25) and irritant (56 [51.9%] vs. 188 [47.7%], P=0.45) patch test reactions. AD patients had significantly higher rates of positive reactions to ingredients in personal care products and topical medications, including fragrance mix II (P=0.04), lanolin (P=0.03), bacitracin (P=0.04), cinnamal (P=0.02), budesonide (P=0.01), tixocortol (P=0.02), and chlorhexidine (P=0.001); relevance was established in >90% of these reactions. Polysensitization occurred more commonly in patients with vs. without AD (35 [32.4%] vs. 75 [19.0%], P=0.01).

Limitations

Study performed at a single center.

Conclusion

AD patients had more positive patch test reactions to ingredients in personal care products, topical steroids and antibiotics.

https://ift.tt/2OhiEC2

Allergic conversion of protective mucosal immunity against nasal bacteria in chronic rhinosinusitis with nasal polyposis

Publication date: Available online 25 July 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): Kazuya Takeda, Shuhei Sakakibara, Kazuo Yamashita, Daisuke Motooka, Shota Nakamura, Marwa Ali El Hussien, Jun Katayama, Yohei Maeda, Masanobu Nakata, Shigeyuki Hamada, Daron M. Standley, Masaki Hayama, Takashi Shikina, Hidenori Inohara, Hitoshi Kikutani

Abstract

Background

Chronic rhinosinusitis with nasal polyposis (CRSwNP) is characterized by eosinophilic inflammation and polyposis at the nose and paranasal sinus and a high concentration of IgE in nasal polyps (NPs). The causative antigen and pathogenesis of CRSwNP remain unknown.

Objective

We aimed to identify reactive allergens of IgE antibodies produced locally in NPs of CRSwNP patients. We also attempted to unravel the differentiation pathway of IgE-producing B cells in the NPs.

Methods

IgE reactivity of CRSwNP patients was investigated by characterizing single cell-derived monoclonal antibodies. T cell response against identified allergens was investigated in vitro. NP-infiltrating lymphocytes were characterized by flow cytometry. Immunoglobulins expressed in NPs were analyzed by high-throughput immunoglobulin (HTS Ig) sequencing.

Results

About 20% of isolated IgE antibodies derived from NP-residing plasmablasts (PBs) specifically recognized surface determinants of nasal bacteria such as Staphylococcus aureus, Streptococcus pyogenes, and Haemophilus influenzae. A Th2 response against S. pyogenes was observed in CRSwNP patients. Flow cytometric analysis revealed sizable germinal center B-like and PB subsets expressing IgE on the cell surface in NPs. HTS Ig analysis highlighted the clonal connectivity of IgE with IgG and IgA₁. The Iε−Cα₁ circle transcript was detected in NPs.

Conclusions

In CRSwNP patients, nasal bacteria-reactive B cells differentiate into IgE-producing B cells through IgG/A₁-IgE class switching, suggesting that allergic conversion of the mucosal response against nasal bacteria underlies disease pathogenesis.

Graphical abstract

https://ift.tt/2NIP3jx

Role of Interleukin-35 in sublingual allergy immunotherapy

Publication date: Available online 25 July 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): Mohamed H. Shamji, Janice A. Layhadi, Daniela Achkova, Lubna Kouser, Alan Perera-Webb, Natália C. Couto-Francisco, Rebecca Parkin, Tomokazu Matsuoka, Guy Scadding, Philip G. Ashton-Rickardt, Stephen R. Durham

ABSTRACT

Background

Grass pollen-specific immunotherapy involves immunomodulation of allergen-specific T helper 2 cell (Th2) responses and induction of IL-10⁺ and/or TGF-β⁺CD4⁺CD25⁺ regulatory T cells (iTregs). IL-35⁺CD4⁺CD25⁺Foxp3^- T (iT_R35) cells have been reported as a novel subset of iTregs with modulatory characteristics.

Objective

To investigate the mechanisms underlying the induction and maintenance of immunological tolerance induced by IL-35 and iT_R35 cells.

Methods

The biological effects of IL-35 was assessed on Group II innate lymphoid cells (ILC2s), dendritic cells (DCs) primed with TSLP, IL-25 and IL-33, B and Th2 cells by flow cytometry and qRT-PCR. Grass pollen-driven Th2 cell proliferation and cytokine production was measured by [³H]-thymidine and Luminex MagPix, respectively. iTr35 cells were quantified in grass pollen allergics (SAR, n=16), sublingual immunotherapy-treated patients (SLIT, n=16) and non-atopic controls (NAC, n=16).

Results

SAR had elevated proportions of ILC2s (P=.002), IL5⁺ (P=.042), IL13⁺ (P=.042) and IL5⁺IL13⁺ILC2s (P=.003) compared to NAC. IL-35 inhibited IL-5 and IL-13 production by ILC2s in the presence of IL-25 or IL-33 (P=.031) and allergen-driven Th2 cytokines by T_eff cells. IL-35 inhibited CD40L, IL-4 and IL-21-mediated IgE production by B cells (P=.015), allergen-driven T cell proliferation (P=.001) and Th2 cytokine production by primed DCs. iT_R35 cells suppressed Th2 cell proliferation and cytokine production. In addition, allergen-driven IL-35 levels and iT_R35 cells were elevated in SLIT (all, P<.001) and NAC (all, P<.001) compared to SAR.

Conclusion

IL-35 and iT_R35 cells are potential novel immune-regulators induced by SLIT. The clinical relevance of SLIT may be underscored by the restoration of protective iT_R35 cells.

Graphical abstract

https://ift.tt/2LzLleQ

Heterotopic Gastrointestinal Cyst of the Oral Cavity Radiology–Pathology Correlation

Abstract

Heterotopic gastrointestinal cyst of the oral cavity is a rare congenital lesion that may arise from ectopic undifferentiated endodermal cells. Imaging, particularly MRI, is useful for surgical planning. On MRI, the cysts typically demonstrate high signal on T2-weighted sequences and variable signal on T1-weighted sequences, which can resemble other conditions, such as dermoids. On histology, the appearance of these lesions can be variable, and may include stratified squamous, simple and ciliated columnar, as well as foveolar and intestinal-type epithelia, often surrounding by smooth muscle. Complete surgical excision is the treatment of choice.

https://ift.tt/2JXVD3o

Clear Cell Odontogenic Carcinoma: Occurrence of EWSR1-CREB1 as Alternative Fusion Gene to EWSR1-ATF1

Abstract

Clear cell odontogenic carcinoma (CCOC) is a rare, low-grade malignant epithelial neoplasm, occurring in the jawbones, mainly affecting the mandible of elderly patients. In addition to hyalinizing clear cell carcinoma of the salivary gland, it is one of the epithelial neoplasms known to harbor an EWSR1-ATF1 fusion. Therefore, a link between these tumors seems plausible. We describe six cases of CCOC showing EWSR1 rearrangements, with two cases being positive for the ATF1 partner gene using FISH analysis. In one case, an EWSR1-CREB1 fusion was identified using RT-PCR, which we report for the first time in this tumor type. The other three cases investigated by FISH were negative for ATF1, CREB1 and CREB3L2. In conclusion, our data show that EWSR1-CREB1 is an alternative fusion gene to EWSR1-ATF1 in CCOC.

https://ift.tt/2mKh7rf

Longevity of composite build-ups without posts—10-year results of a practice-based study

Abstract

Aim

The aim of this prospective, non-interventional, multi-center, practice-based study was, firstly, to evaluate the longevity of composite build-ups in endodontically treated teeth (ETT) without post placement and, secondly, to analyze factors influencing the success of these composite build-ups.

Methodology

Each of seven general dental practitioners placed up to 50 composite build-ups without additional posts in ETT. Teeth were restricted to incisors, canines, and premolars. Several clinical data were recorded for 192 coronal restorations on ETT in 192 patients. Cox proportional hazard models were applied to analyze associations between clinical factors and time until failure.

Results

Within a follow-up period of 10 years, 167 restorations were judged as successful [mean success time, 110 (105–115) months] and 180 teeth survived [mean survival time, 114 (110–119) months]. The main failure type was fracture of the restoration (n = 15). The annual failure rate was 2.4%. In bivariate Cox regression, both factors such as number of restored tooth surfaces and adhesive were significantly associated with the failure rate. In multivariate Cox proportional hazards regression, none of the investigated factors were significantly associated with the failure rate.

Conclusion

For composite build-ups in ETT without post placement, high success rates could be found after up to 10 years of observation time. Within the limitations of the present study, none of the analyzed factors such as "tooth type" or "number of restored tooth surfaces" was a significant predictor for the failure rate.

Clinical relevance

Endodontically treated teeth can be successfully directly restored with composite build-ups even when no additional post is inserted.

Trial registration

The study was registered in the German Clinical Trials Register (DRKS-ID: DRKS00012882).

https://ift.tt/2v0gXjx