Research

Rheumatologic manifestations of primary immunodeficiency diseases.

Clin Rheumatol. 2016 Mar 14;

Authors: Dimitriades VR, Sorensen R

Abstract
In the last 5 years, several hundred articles have been published concerning the link between primary immunodeficiency disease (PID) and rheumatologic diseases. Although rheumatologic complications were originally thought to be at the opposite ends of the spectrum of immunopathologic manifestations, they are now all being considered secondary manifestations of a causative primary “immune derangement.” For the rheumatologist, it is important to be able to identify patients who may present with typical rheumatologic findings but who have an underlying PID. In a systematic manner, this overview addresses both the systemic and organ-based rheumatologic diseases which have known associations with primary immunodeficiencies, and explores how immunodeficiency may actually cause these clinical manifestations.

PMID: 26971790 [PubMed – as supplied by publisher]

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IL-21 Signaling in Immunity.

F1000Res. 2016;5

Authors: Leonard WJ, Wan CK

Abstract
IL-21 is a type I cytokine produced by T cells and natural killer T cells that has pleiotropic actions on a wide range of immune and non-immune cell types. Since its discovery in 2000, extensive studies on the biological actions of IL-21 have been performed in vitro and in vivo. Recent reports describing patients with primary immunodeficiency caused by mutations of IL21 or IL21R have further deepened our knowledge of the role of this cytokine in host defense. Elucidation of the molecular mechanisms that mediate IL-21’s actions has provided the rationale for targeting IL-21 and IL-21 downstream mediators for therapeutic purposes. The use of next-generation sequencing technology has provided further insights into the complexity of IL-21 signaling and has identified transcription factors and co-factors involved in mediating the actions of this cytokine. In this review, we discuss recent advances in the biology and signaling of IL-21 and how this knowledge can be potentially translated into clinical settings.

PMID: 26966515 [PubMed]

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Human T Follicular Helper Cells in Primary Immunodeficiency: Quality Just as Important as Quantity.

J Clin Immunol. 2016 Mar 10;

Authors: Ma CS

Abstract
T follicular helper (Tfh) cells are a subset of effector CD4(+) T cells specialised to induce Ab production by B cells. This review highlights some of the recent advances in the field of human Tfh cells that have come from the study of primary immunodeficiencies. In particular it is increasingly evident that the quality of the Tfh cells that are generated, is just as important as the quantity.

PMID: 26961358 [PubMed – as supplied by publisher]

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Griscelli syndrome type 2: A rare and fatal syndrome in a South Indian boy.

Indian J Pathol Microbiol. 2016 Jan-Mar;59(1):113-6

Authors: Rajyalakshmi R, Chakrapani RN

Abstract
Griscelli syndrome (GS) is a rare autosomal recessive disorder caused by mutation in the MYO5A (GS1), RAB27A (GS2), and MLPH (GS3) genes, characterized by a common feature, partial albinism. The common variant of three, GS type 2, in addition, shows primary immunodeficiency which leads to recurrent infections and hemophagocytic lymphohistiocytosis. We, herewith, describe a case of GS type 2, in a 4-year-old male child who presented with chronic and recurrent fever, lymphadenopathy, hepatosplenomegaly, and secondary neurological deterioration; highlighting the cytological and histopathological features of lymph nodes. Hair shaft examination of the child confirmed the diagnosis.

PMID: 26960655 [PubMed – in process]

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Evaluation of Known Defective Signaling-Associated Molecules in Patients Who Primarily Diagnosed as Common Variable Immunodeficiency.

Int Rev Immunol. 2016 Jan 2;35(1):7-24

Authors: Yazdani R, Abolhassani H, Rezaei N, Azizi G, Hammarström L, Aghamohammadi A

Abstract
Common variable immunodeficiency (CVID) is a primary immunodeficiency disease, associated with defective antibody production and recurrent infections. Several defective signaling-associated molecules related to B-cell receptor, T-cell receptor, toll-like receptor, and other immune cell-associated receptors have been identified so far. In this review, defects of cell signaling associated molecules at three levels of surface cytoplasmic, and nuclear molecules are highlighted in patients who primarily diagnosed as CVID. It could be suggested that impaired cell signaling may be involved in the pathogenesis of CVID.

PMID: 26959802 [PubMed – as supplied by publisher]

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Sinopulmonary Complications in Subjects With Primary Immunodeficiency.

Respir Care. 2016 Mar 8;

Authors: Owayed A, Al-Herz W

Abstract
BACKGROUND: The aim of this work was to describe the frequency and spectrum of sinopulmonary complications among subjects with primary immunodeficiency disorders.
METHODS: The subjects included all patients with primary immunodeficiency who were registered prospectively between January 2004 and December 2013 in the Kuwait National Primary Immunodeficiency Disorders Registry.
RESULTS: A total of 202 subjects were registered during the study period. Subjects with combined immunodeficiencies were the most prevalent (65 subjects, 32.1%), followed by well-defined syndromes with immunodeficiency (45 subjects, 22.2%) and predominantly antibody deficiencies (35 subjects, 17.3%). A total of 295 sinopulmonary manifestations were observed in 127 subjects (63%); 157 manifestations (53.2%) were observed among the presenting symptoms, and 138 manifestations (46.8%) occurred after establishment of the primary immunodeficiency disorder diagnosis. Sinopulmonary manifestations were more common in subjects with predominantly antibody deficiencies (2.3 manifestations/subject), followed by subjects with combined immunodeficiencies (1.75 manifestations/subject). Pneumonia was the most common manifestation (108 episodes affecting 80 subjects), followed by otitis media (81 episodes affecting 59 subjects), bronchiectasis in 28 subjects (13.8%), and asthma in 22 subjects (11%). Microbial organisms were isolated during 46 episodes of pneumonia (42.5%) (cytomegalovirus and Pneumocystis jirovecii were the most common). There were 57 deaths (28%) during the study period. Twenty-four deaths (42%) were due to pulmonary complications as follows: pneumonia (16 subjects, 8%), pulmonary hemorrhage (6 subjects, 3%), and aspiration pneumonia (2 subjects, 1%).
CONCLUSIONS: Sinopulmonary complications are common in subjects with primary immunodeficiency. They can be serious and continue to occur even after proper treatment is initiated. The pulmonologist should play an important role in the management of subjects with primary immunodeficiency disorder.

PMID: 26957648 [PubMed – as supplied by publisher]

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Strain-specific loss of formyl peptide receptor 3 in the murine vomeronasal and immune systems.

J Biol Chem. 2016 Mar 8;

Authors: Stempel H, Jung M, Pérez-Goméz A, Leinders-Zufall T, Zufall F, Bufe B

Abstract
Formyl peptide receptor 3 (Fpr3, also known as Fpr-rs1) is a G protein-coupled receptor expressed in subsets of sensory neurons of the mouse vomeronasal organ, an olfactory substructure essential for social recognition. Fpr3 has been implicated in the sensing of infection-associated olfactory cues but its expression pattern and function are incompletely understood. To facilitate visualization of Fpr3-expressing cells, we generated and validated two new anti-Fpr3 antibodies enabling us to analyze acute Fpr3 protein expression. Fpr3 is not only expressed in murine vomeronasal sensory neurons but also in bone marrow cells, the primary source for immune cell renewal, and in mature neutrophils. Consistent with the notion that Fpr3 functions as a pathogen sensor, Fpr3 expression in the immune system is upregulated after stimulation with a bacterial endotoxin (lipopolysaccharide). These results strongly support a dual role for Fpr3 in both vomeronasal sensory neurons and immune cells. We also identify a large panel of mouse strains with severely altered expression and function of Fpr3, thus establishing the existence of natural Fpr3 knockout strains. We attribute distinct Fpr3 expression in these strains to the presence or absence of a 12 nucleotide in-frame deletion (Fpr3Δ424-435). In vitro calcium imaging and immunofluorescence analyses demonstrate that the lack of four amino acids leads to an unstable, truncated and non-functional receptor protein. The genome of at least 19 strains encodes a non-functional Fpr3 variant whereas at least 13 other strains express an intact receptor. These results provide a foundation for understanding the in vivo function of Fpr3.

PMID: 26957543 [PubMed – as supplied by publisher]

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Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia.

Nat Commun. 2016;7:10933

Authors: Berndt SI, Camp NJ, Skibola CF, Vijai J, Wang Z, Gu J, Nieters A, Kelly RS, Smedby KE, Monnereau A, Cozen W, Cox A, Wang SS, Lan Q, Teras LR, Machado M, Yeager M, Brooks-Wilson AR, Hartge P, Purdue MP, Birmann BM, Vajdic CM, Cocco P, Zhang Y, Giles GG, Zeleniuch-Jacquotte A, Lawrence C, Montalvan R, Burdett L, Hutchinson A, Ye Y, Call TG, Shanafelt TD, Novak AJ, Kay NE, Liebow M, Cunningham JM, Allmer C, Hjalgrim H, Adami HO, Melbye M, Glimelius B, Chang ET, Glenn M, Curtin K, Cannon-Albright LA, Diver WR, Link BK, Weiner GJ, Conde L, Bracci PM, Riby J, Arnett DK, Zhi D, Leach JM, Holly EA, Jackson RD, Tinker LF, Benavente Y, Sala N, Casabonne D, Becker N, Boffetta P, Brennan P, Foretova L, Maynadie M, McKay J, Staines A, Chaffee KG, Achenbach SJ, Vachon CM, Goldin LR, Strom SS, Leis JF, Weinberg JB, Caporaso NE, Norman AD, De Roos AJ, Morton LM, Severson RK, Riboli E, Vineis P, Kaaks R, Masala G, Weiderpass E, Chirlaque MD, Vermeulen RC, Travis RC, Southey MC, Milne RL, Albanes D, Virtamo J, Weinstein S, Clavel J, Zheng T, Holford TR, Villano DJ, Maria A, Spinelli JJ, Gascoyne RD, Connors JM, Bertrand KA, Giovannucci E, Kraft P, Kricker A, Turner J, Ennas MG, Ferri GM, Miligi L, Liang L, Ma B, Huang J, Crouch S, Park JH, Chatterjee N, North KE, Snowden JA, Wright J, Fraumeni JF, Offit K, Wu X, de Sanjose S, Cerhan JR, Chanock SJ, Rothman N, Slager SL

Abstract
Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and 7,667 controls with follow-up replication in 1,958 cases and 5,530 controls. Here we report three new loci at 3p24.1 (rs9880772, EOMES, P=2.55 × 10(-11)), 6p25.2 (rs73718779, SERPINB6, P=1.97 × 10(-8)) and 3q28 (rs9815073, LPP, P=3.62 × 10(-8)), as well as a new independent SNP at the known 2q13 locus (rs9308731, BCL2L11, P=1.00 × 10(-11)) in the combined analysis. We find suggestive evidence (P<5 × 10(-7)) for two additional new loci at 4q24 (rs10028805, BANK1, P=7.19 × 10(-8)) and 3p22.2 (rs1274963, CSRNP1, P=2.12 × 10(-7)). Pathway analyses of new and known CLL loci consistently show a strong role for apoptosis, providing further evidence for the importance of this biological pathway in CLL susceptibility.

PMID: 26956414 [PubMed – in process]

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[Clinical analysis of 16 cases of invasive pulmonary aspergillosis in children].

Zhonghua Er Ke Za Zhi. 2016 Mar 2;54(3):187-91

Authors: Li Y, Nong GM, Jiang M, Liu J, Liang XA

Abstract
OBJECTIVE: To investigate the diagnosis and treatment of invasive pulmonary aspergillosis (IPA) in children.
METHOD: The clinical data of 16 cases of proven or probable IPA who had been in our Hospital from January 2006 to June 2014 were retrospectively analyzed.
RESULT: Among the 16 patients, 11 were males and 5 were females. One child had proven IPA and 15 children had probable IPA. Host risk included long duration use of multiple broad-spectrum antibiotics in 16 cases, neutropenia in 9 cases, invasive mechanical ventilation in 3 cases, primary immunodeficiency disease in 2 cases, long-term use of glucocorticoids in 2 cases, measles in 2 cases, and congenital pulmonary hypoplasia in 1 case. Fever, cough and expectoration were present in all the children with IPA. At the time of diagnosis, the halo sign and subpleural wedge consolidation shadows were more common in neutropenia group (5/9, 7/9) than those in non-neutropenia group(0/7, 1/7)(P<0.05). The cavities and”air-crescent sign”were more common after 15 days to 1 month when the children had been treated with anti-aspergillosis drugs than that at the onset of diagnosis of IPA (P<0.05). The positive rate of serum galactomannan (GM) test was higher than that of sputum culture and serum G test (P<0.05). Thirteen children received voriconazole, in 7 of the children the treatment was effective.
CONCLUSION: Neutropenia were the common host risk factors in children with IPA. Subpleural wedge consolidation shadows, the halo sign and the”air-crescent”sign were highly suggestive of the diagnosis of IPA in children. Subpleural wedge consolidation shadows and the halo sign were more common in neutropenia group than in non-neutropenia group in the early stage of the course. Serum GM test played an important role in the diagnosis of IPA in children. Voriconazole was effective in majority of the children with IPA.

PMID: 26957063 [PubMed – in process]

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Presenting features and platelet anomalies in WAS: one centre’s experience.

J Clin Immunol. 2016 Mar 7;

Authors: Tsilifis C, Gennery AR, Cant A

PMID: 26951488 [PubMed – as supplied by publisher]

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