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IgA deficiency in wolves from Canada and Scandinavia.

Dev Comp Immunol. 2014 Dec 18;

Authors: Frankowiack M, Olsson M, Cluff HD, Evans AL, Hellman L, Månsson J, Arnemo JM, Hammarström L

Abstract
Immunoglobulin A deficiency (IgAD) is the most common primary immunodeficiency in both humans and selected breeds of domestic dogs. In both species, IgAD is associated with recurrent infections and immune mediated diseases. Previous results imply that IgAD is also common in the wild ancestor of domestic dogs, the gray wolf. Here, we report that serum IgA concentrations are significantly different in Scandinavian and Canadian wolves (p=3.252e-15) with an increased prevalence for IgAD in Scandinavian wolves (60 %), which is as high as those found in high-risk dog breeds.

PMID: 25530092 [PubMed – as supplied by publisher]

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Diagnosing Primary Immunodeficiency: A Practical Approach for the Non-immunologist.

Curr Med Res Opin. 2014 Dec 22;:1-23

Authors: Lehman H, Hernandez-Trujillo V, Ballow M

Abstract
Abstract Objective: This review will provide an overview of the most common clinical presentations of primary immunodeficiency (PI), navigating through various affected organ systems. The goal is to accurately portray the high variability of this disease and provide a resource that helps to raise the index of suspicion of PI among physicians, aid in recognition of various PI disorders, and trigger more frequent screenings with appropriate referrals to immunologists for further evaluation and treatment. Summary: Patients with PI comprise more than 200 defined genetic abnormalities. Patients have an array of clinical manifestations, ranging from the most widely-associated recurrent and chronic bacterial infections to other associated comorbid conditions involving many organ systems. There is still considerable delay between the onset of symptoms and the time of diagnosis of PI. This review will present an overview of the clinical manifestations that will enhance a physician’s recognition of a possible PI. Particular emphasis is placed on the pathogens associated with the specific arm of the immune system that is related to each particular type of PI. The initial immune evaluation is described, which together with the history and physical exam can help focus the physician on the immune compartment most likely associated with a PI. Conclusions: Understanding the types of PI and the related clinical manifestations can help physicians see beyond the presenting symptoms and lead to improved recognition and diagnosis of PI. Timely diagnosis is of utmost importance in PI, as recent advances in bone transplantation and immunoglobulin replacement therapy, as well as future gene therapies, provide effective ways to prevent significant mortality and morbidity.

PMID: 25530045 [PubMed – as supplied by publisher]

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Dynamics of perinatal bovine leukemia virus infection.

BMC Vet Res. 2014;10:82

Authors: Gutiérrez G, Alvarez I, Merlini R, Rondelli F, Trono K

Abstract
BACKGROUND: Bovine leukemia virus (BLV) is highly endemic in many countries, including Argentina. As prevention of the spread from infected animals is of primary importance in breaking the cycle of BLV transmission, it is important to know the pathophysiology of BLV infection in young animals, as they are the main source of animal movement. In this work, we determined the proviral load and antibody titers of infected newborn calves from birth to first parturition (36 months).
RESULTS: All calves under study were born to infected dams with high proviral load (PVL) in blood and high antibody titers and detectable provirus in the colostrum. The PVL for five out of seven calves was low at birth. All animals reached PVLs of more than 1% infected peripheral blood mononuclear cells (PBMCs), three at 3 months, one at 6 months, and one at 12 months. High PVLs persisted until the end of the study, and, in two animals, exceeded one BLV copy per cell. Two other calves maintained a high PVL from birth until the end of the study. Antibody titers were 32 or higher in the first sample from six out of seven calves. These decayed at 3-6 months to 16 or lower, and then increased again after this point.
CONCLUSIONS: Calves infected during the first week of life could play an active role in early propagation of BLV to susceptible animals, since their PVL raised up during the first 12 months and persist as high for years. Early elimination could help to prevent transmission to young susceptible animals and to their own offspring. To our knowledge, this is the first study of the kinetics of BLV proviral load and antibody titers in newborn infected calves.

PMID: 24708791 [PubMed – indexed for MEDLINE]

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[Diagnostics of ataxia-telangiectasia by the express-test found on the method of indirect immunofluorescence].

Tsitologiia. 2013;55(8):560-5

Authors: Kuranova ML, Ledashcheva TA, Tulush EK, Beliaev DL, Zherebtsov SV, Pleskach NM, Prokof’eva VV, Mikhel’son VM, Spivak IM

Abstract
Ataxia-telangiectasia (AT) is a hereditary severe neurodegenerative disease developing, when mutations take place in both alleles of the atm gene, which encodes the key protein of the cellular response to DNA damage (DDR)–ATM proteinkinase. In response to the occurrence of double-strand DNA breaks, the ATM proteinkinase pass the autophosphorylation, and its active form–the phospho-ATM (P-ATM) appears in cells. In the nuclei of cells having the atm gene, P-ATM is revealed, being absent in cells with mutated forms of this gene, by means of the application of the modified method of indirect immunofluorescence. This peculiarity may be applied in the clinic, in order to confirm the diagnosis of AT.

PMID: 25486788 [PubMed – indexed for MEDLINE]

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Disseminated Bacille Calmette – Guerin (BCG) Disease in an Infant with Severe Combined Immunodeficiency.

J Coll Physicians Surg Pak. 2014 Nov;24(11):S259-S261

Authors: Sohail S, Afzal M, Anwar V, Shama Q

Abstract
Bacille Calmette-Guerin (BCG) vaccine is administered to all newborns in countries where tuberculosis is still endemic. It is a live attenuated vaccine and considered quite safe in immunocompetent children. Disseminated BCG disease is the most serious complication seen only in individuals with underlying primary or secondary immunodeficiencies. We report a case of disseminated BCG disease in an infant with Severe Combined Immunodeficiency (SCID) who received BCG administration prior to diagnosis of SCID.

PMID: 25518795 [PubMed – as supplied by publisher]

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Acute Disseminated Encephalomyelitis: An Uncommon Presentation of Hyper IgE Syndrome.

J Coll Physicians Surg Pak. 2014 Nov;24(11):S256-S258

Authors: Purkait R, Kar S, Bhadra R, Sinhamahapatra T

Abstract
The hyper-immunoglobulin E (IgE) syndrome (HIES), also known as Job’s syndrome is a rare primary immunodeficiency characterized by the clinical triad of recurrent staphylococcal abscesses of skin, recurrent cyst-forming pneumonia, and an elevated serum IgE level of > 2000 IU/ml. Although, most cases are sporadic, families with autosomal dominant (AD-HIES) and recessive (AR-HIES) traits have been reported. Very few articles were published previously on central nervous system abnormalities with definite neurologic manifestations which may vary from partial facial nerve paralysis to hemiplegia in children but Acute Disseminated Encephalomyelitis (ADEM) in a child with HIES hitherto has not been reported. Here we describe a 5-year-old male child with HIES who presented with neurologic manifestations of ADEM.

PMID: 25518794 [PubMed – as supplied by publisher]

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Unrelated donor cord blood transplantation for non-malignant disorders in children and adolescents.

Pediatr Transplant. 2014 Mar;18(2):221-9

Authors: Park M, Lee YH, Kang HR, Lee JW, Kang HJ, Park KD, Shin HY, Ahn HS, Baek HJ, Kook H, Hwang TJ, Lee JW, Chung NG, Cho B, Kim HK, Lee SH, Yoo KH, Sung KW, Koo HH, Koh KN, Im HJ, Seo JJ, Park JE, Lim YJ, Lyu CJ, Lee JM, Hah JO, Korean Cord Blood Transplantation Working Party

Abstract
This study analyzes the data reported to the Korean Cord Blood Registry between 1994 and 2008, involving children and adolescents with non-malignant diseases. Sixty-five patients were evaluated in this study: SAA (n = 24), iBMFS, (n = 16), and primary immune deficiency/inherited metabolic disorder (n = 25). The CI of neutrophil recovery was 73.3% on day 42. By day 100, the CI of acute grade II-IV graft-versus-host disease was 32.3%. At a median follow-up of 71 months, five-yr OS was 50.7%. The survival rate (37.5%) and CI of neutrophil engraftment (37.5%) were lowest in patients with iBMFS. Deaths were mainly due to infection, pulmonary complications, and hemorrhage. In a multivariate analysis, the presence of >3.91 × 10(5) /kg of infused CD34 + cells was the only factor consistently identified as significantly associated with neutrophil engraftment (p = 0.04) and OS (p = 0.03). UCBT using optimal cell doses appears to be a feasible therapy for non-malignant diseases in children and adolescents for whom there is no appropriate HLA-matched related donor. Strategies to reduce transplant-related toxicities would improve the outcomes of UCBT in non-malignant diseases.

PMID: 24372660 [PubMed – indexed for MEDLINE]

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Identification of Patients with RAG Mutations Previously Diagnosed with Common Variable Immunodeficiency Disorders.

J Clin Immunol. 2014 Dec 17;

Authors: Buchbinder D, Baker R, Lee YN, Ravell J, Zhang Y, McElwee J, Nugent D, Coonrod EM, Durtschi JD, Augustine NH, Voelkerding KV, Csomos K, Rosen L, Browne S, Walter JE, Notarangelo LD, Hill HR, Kumánovics A

Abstract
PURPOSE: Combined immunodeficiency (CID) presents a unique challenge to clinicians. Two patients presented with the prior clinical diagnosis of common variable immunodeficiency (CVID) disorder marked by an early age of presentation, opportunistic infections, and persistent lymphopenia. Due to the presence of atypical clinical features, next generation sequencing was applied documenting RAG deficiency in both patients.
METHODS: Two different genetic analysis techniques were applied in these patients including whole exome sequencing in one patient and the use of a gene panel designed to target genes known to cause primary immunodeficiency disorders (PIDD) in a second patient. Sanger dideoxy sequencing was used to confirm RAG1 mutations in both patients.
RESULTS: Two young adults with a history of recurrent bacterial sinopulmonary infections, viral infections, and autoimmune disease as well as progressive hypogammaglobulinemia, abnormal antibody responses, lymphopenia and a prior diagnosis of CVID disorder were evaluated. Compound heterozygous mutations in RAG1 (1) c256_257delAA, p86VfsX32 and (2) c1835A>G, pH612R were documented in one patient. Compound heterozygous mutations in RAG1 (1) c.1566G>T, p.W522C and (2) c.2689C>T, p. R897X) were documented in a second patient post-mortem following a fatal opportunistic infection.
CONCLUSION: Astute clinical judgment in the evaluation of patients with PIDD is necessary. Atypical clinical findings such as early onset, granulomatous disease, or opportunistic infections should support the consideration of atypical forms of late onset CID secondary to RAG deficiency. Next generation sequencing approaches provide powerful tools in the investigation of these patients and may expedite definitive treatments.

PMID: 25516070 [PubMed – as supplied by publisher]

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Poliovirus excretion among persons with primary immune deficiency disorders: summary of a seven-country study series.

J Infect Dis. 2014 Nov 1;210 Suppl 1:S368-72

Authors: Li L, Ivanova O, Driss N, Tiongco-Recto M, da Silva R, Shahmahmoodi S, Sazzad HM, Mach O, Kahn AL, Sutter RW

Abstract
BACKGROUND: Persons with primary immune deficiency disorders (PID), especially those disorders affecting the B-cell system, are at substantially increased risk of paralytic poliomyelitis and can excrete poliovirus chronically. However, the risk of prolonged or chronic excretion is not well characterized in developing countries. We present a summary of a country study series on poliovirus excretion among PID cases.
METHODS: Cases with PID from participating institutions were enrolled during the first year and after obtaining informed consent were tested for polioviruses in stool samples. Those cases excreting poliovirus were followed on a monthly basis during the second year until 2 negative stool samples were obtained.
RESULTS: A total of 562 cases were enrolled in Bangladesh, China, Iran, Philippines, Russia, Sri Lanka, and Tunisia during 2008-2013. Of these, 17 (3%) shed poliovirus, including 2 cases with immunodeficient vaccine-derived poliovirus. Poliovirus was detected in a single sample from 5/17 (29%) cases. One case excreted for more than 6 months. None of the cases developed paralysis during the study period.
CONCLUSIONS: Chronic polioviruses excretion remains a rare event even among individuals with PID. Nevertheless, because these individuals were not paralyzed they would have been missed by current surveillance; therefore, surveillance for polioviruses among PID should be established.

PMID: 25316857 [PubMed – indexed for MEDLINE]

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Primary immunodeficiencies: a decade of shifting paradigms, the current status and the emergence of cutting-edge therapies and diagnostics.

Expert Rev Clin Immunol. 2014 Dec 16;:1-23

Authors: Ebadi M, Aghamohammadi A, Rezaei N

Abstract
A shift has occurred in the diagnostic and therapeutic modalities considered for patients with primary immunodeficiency diseases (PIDs). Early diagnosis remains the mainstay in appropriate management and remarkably influences the prognosis. More specific diagnostic tests as well as therapeutic modalities have been introduced in the last few decades. Nonetheless, the importance of a thorough history taking and physical examination should not be neglected. Novel diagnostic modalities including genetic sequencing have led to the recognition of previously unknown defects underlying PIDs. In addition, newborn screening is being advocated as an imperative diagnostic test. In terms of treatment, hematopoietic stem cell transplantation is considered the optimal treatment modality for many cases and has dramatically improved the outcome. Gene transfer into hematopoietic stem cells prior to transplantation has improved the efficacy of hematopoietic stem cell transplantation. In this article, the latest advances made in terms of diagnosis and treatment of PIDs are reviewed.

PMID: 25511261 [PubMed – as supplied by publisher]

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