Research

Hematopoietic stem cell transplantation for CTLA4 deficiency.

J Allergy Clin Immunol. 2016 Apr 18;

Authors: Slatter MA, Engelhardt KR, Burroughs LM, Arkwright PD, Nademi Z, Skoda-Smith S, Hagin D, Kennedy A, Barge D, Flood T, Abinun M, Wynn RF, Gennery AR, Cant AJ, Sansom D, Hambleton S, Torgerson TR

PMID: 27102614 [PubMed – as supplied by publisher]

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Incidence of the C104R TACI Mutation in Patients With Primary Antibody Deficiency.

J Investig Allergol Clin Immunol. 2015;25(5):378-9

Authors: Lucena JM, Burillo Sanz S, Núñez-Roldan A, Sánchez B

PMID: 26727773 [PubMed – indexed for MEDLINE]

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Primary immunodeficiency for the primary care provider.

Paediatr Child Health. 2016 Mar;21(2):e10-4

Authors: O’Keefe AW, Halbrich M, Ben-Shoshan M, McCusker C

Abstract
Primary immunodeficiencies are a group of heterogeneous disorders resulting from defects affecting the function of ≥1 parts of the immune system. Current estimates of the prevalence of primary immunodeficiency disease are one in 1200 patients. In Ontario, where the average general practitioner follows 1300 to 2000 patients, an estimated two patients will have primary immunodeficiency. With new primary immunodeficiencies being described at an exponential rate, and those previously described becoming better understood, it is challenging for health care providers to stay up to date. Knowledge gaps delay diagnosis and treatment, leading to increased morbidity and mortality. The present review aims to provide the primary care provider with the tools necessary to recognize primary immunodeficiency and assist in establishing diagnoses.

PMID: 27095888 [PubMed]

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The ABCs of Immunosuppression: A Primer for Primary Care Physicians.

Med Clin North Am. 2016 May;100(3):505-18

Authors: Malat G, Culkin C

Abstract
Immunosuppression use for prevention of allograft recognition/rejection has evolved to reflect an expanded understanding of the immune system, as well as a fine tuning of the goals of therapy. Immunosuppression in organ transplantation represents a balance between the desire to improve the health status of an individual affected by chronic conditions versus not imposing an unintended immunodeficiency leading to iatrogenic morbidity/mortality. This article discusses the selection and general dosing of immunosuppression in organ allograft recipients to allow providers to be comfortable in monitoring immunosuppressive therapy long term and the associated, expected posttransplant complications in allograft recipients.

PMID: 27095642 [PubMed – in process]

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Clinical laboratory standard capillary protein electrophoresis alerted of a low C3 state and lead to the identification of a factor I deficiency due to a novel homozygous mutation.

Immunol Lett. 2016 Apr 14;

Authors: Franco-Jarava C, Colobran R, Mestre-Torres J, Vargas V, Pujol-Borrell R, Hernández-González M

Abstract
Complement factor I (CFI) deficiency is typically associated to recurrent infections with encapsulated microorganisms and, less commonly, to autoimmunity. We report a 53-years old male who, in a routine control for non-alcoholic fatty liver disease, presented a flat beta-2 fraction at the capillary protein electropherogram. Patient’s clinical records included multiple oropharyngeal infections since infancy and an episode of invasive meningococcal infection. Complement studies revealed reduced C3, low classical pathway activation and undetectable Factor I. CFI gene sequencing showed a novel inherited homozygous deletion of 5 nucleotides in exon 12, causing a frameshift leading to a truncated protein. This study points out that capillary protein electrophoresis can alert of possible states of low C3, which, once confirmed and common causes ruled out, can lead to CFI and other complement deficiency diagnosis. This is important since they constitute a still underestimated risk of invasive meningococcemia that can be greatly reduced by vaccination.

PMID: 27091480 [PubMed – as supplied by publisher]

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Mechanistic Insights into the Role of C-Type Lectin Receptor/CARD9 Signaling in Human Antifungal Immunity.

Front Cell Infect Microbiol. 2016;6:39

Authors: Drummond RA, Lionakis MS

Abstract
Human CARD9 deficiency is an autosomal recessive primary immunodeficiency disorder caused by biallelic mutations in the gene CARD9, which encodes a signaling protein that is found downstream of many C-type lectin receptors (CLRs). CLRs encompass a large family of innate recognition receptors, expressed predominantly by myeloid and epithelial cells, which bind fungal carbohydrates and initiate antifungal immune responses. Accordingly, human CARD9 deficiency is associated with the spontaneous development of persistent and severe fungal infections that primarily localize to the skin and subcutaneous tissue, mucosal surfaces and/or central nervous system (CNS). In the last 3 years, more than 15 missense and nonsense CARD9 mutations have been reported which associate with the development of a wide spectrum of fungal infections caused by a variety of fungal organisms. The mechanisms by which CARD9 provides organ-specific protection against these fungal infections are now emerging. In this review, we summarize recent immunological and clinical advances that have provided significant mechanistic insights into the pathogenesis of human CARD9 deficiency. We also discuss how genetic mutations in CARD9-coupled receptors (Dectin-1, Dectin-2) and CARD9-binding partners (MALT1, BCL10) affect human antifungal immunity relative to CARD9 deficiency, and we highlight major understudied research questions which merit future investigation.

PMID: 27092298 [PubMed – in process]

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Health-Related Quality of Life and Health Resource Utilization in Patients with Primary Immunodeficiency Disease Prior to and Following 12 Months of Immunoglobulin G Treatment.

J Clin Immunol. 2016 Apr 18;

Authors: Routes J, Costa-Carvalho BT, Grimbacher B, Paris K, Ochs HD, Filipovich A, Hintermeyer M, de Melo KM, Workman S, Ito D, Ye X, Bonnet P, Li-McLeod J

Abstract
PURPOSE: Health-related quality of life (HRQOL) has not been examined in patients with predominant antibody deficiency both pre- and post-immunoglobulin G (IgG) treatment initiation. HRQOL and health resource utilization (HRU) were assessed in newly diagnosed patients with primary immunodeficiency disease (PIDD) pre- and 12 months post-IgG treatment initiation.
METHODS: Adults (age ≥18 years) completed the 36-item Short Form Health Survey, version 2; pediatric patients (PP)/caregivers completed the Pediatric Quality of Life Inventory (PedsQL). Scores were compared with normative data from the US general population (GP) and patients with other chronic conditions (OCC).
RESULTS: Seventeen adult patients (APs), 8 PPs, and 8 caregivers completed baseline assessments. APs had significantly lower baseline mean physical component summary scores versus GP (37.4 vs 50.5, p < 0.01) adults with chronic back pain (44.1, p < 0.05) or cancer (44.4, p < 0.05) and lower mental component summary scores versus GP (41.6 vs 49.2, p < 0.05). PPs had lower PedsQL total (63.1 vs 82.7), physical summary (64.5 vs 84.5), and psychosocial summary (62.5 vs 81.7) scores versus GP. Post-IgG treatment, 14 APs, 6 PPs, and 8 caregivers completed assessments. Hospital admissions (0.2 versus 1.8, p < 0.01), serious infections (3.3 versus 10.9, p < 0.01) and antibiotic prescriptions (3.0 versus 7.1; p < 0.01) decreased significantly overall. While APs reported significant improvement in role-physical (p = 0.01), general health (p < 0.01), and social functioning (p = 0.02) and caregivers in vitality (p < 0.01), PPs did not.
CONCLUSIONS: Pre-IgG treatment, patients with PIDD experienced diminished HRQOL versus GP and patients with OCC; post-treatment, HRU decreased and certain HRQOL aspects improved for APs and caregivers.

PMID: 27091140 [PubMed – as supplied by publisher]

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Zellweger syndrome with severe malnutrition, immunocompromised state and opportunistic infections.

BMJ Case Rep. 2016;2016

Authors: Cardoso P, Amaral ME, Lemos S, Garcia P

Abstract
Peroxisome biogenesis disorders are related to a spectrum of genetic diseases that range from severe Zellweger syndrome to milder infantile Refsum disease. Zellweger syndrome is characterised by dysmorphic features, severe hypotonia, seizures, failure to thrive, liver dysfunction and skeletal defects. Increased levels of very long chain fatty acids are the biochemical hallmark and the most common mutations found in the PEX1 gene. We report an unusual presentation of Zellweger syndrome in a 2-month-old female infant with severe malnutrition, opportunistic infections, lymphopaenia and a small thymic shadow on chest radiography. With this clinical picture, an initial hypothesis of primary immunodeficiency was considered. It was later confirmed to not be the case. On follow-up, global developmental delay, bilateral optic nerve atrophy and moderate bilateral sensorineural deafness grade II were documented. There were no further infectious complications and we concluded malnutrition was the cause of the infant’s immunocompromised state.

PMID: 27090541 [PubMed – in process]

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A prospective ten-year follow-up of patients with chronic urticaria.

Allergol Immunopathol (Madr). 2016 Apr 12;

Authors: Dionigi PC, Menezes MC, Forte WC

Abstract
BACKGROUND: Chronic urticaria can be the initial clinical presentation of a number of different diseases. The objective of the present study was to report the associated diseases during a ten-year clinical-laboratory follow-up in patients with an initial diagnosis of chronic spontaneous urticaria (CSU) of unknown cause.
METHODS: A prospective, longitudinal cohort study with a ten-year clinical-laboratory follow-up was conducted. Patients with a history of urticarial plaques of over six weeks presenting as the only clinical symptom were selected. Individuals with other clinical conditions, urticaria of known causes or chronic physical urticaria were excluded. The following tests were initially performed: haemogram, urine type I, stool parasite exam and sedimentation rate. The following exams were ordered during follow-up: PPD; urine culture; serology tests; antithyroid and antinuclear antibodies, rheumatoid factor, lupus anticoagulant; thyroid hormones; serum immunoglobulin; paranasal sinus and thorax radiographs; testing for BK and Helicobacter pylori; and prick tests.
RESULTS: Infections were diagnosed in 29% of patients (syphilis, parasitosis, H. pylori, urinary infection, tuberculosis, hepatitis B and C); autoimmune diseases in 21% (thyroiditis, rheumatoid arthritis and antiphospholipid antibody syndrome); primary immunodeficiencies in 4% (IgA and IgG2 deficiencies); and chronic myeloid leukaemia in 1%. At ten-years of follow-up, the urticaria diagnosis was CSU of unknown cause in 45% of the cases.
CONCLUSION: This ten-year clinical-laboratory follow-up of 100 individuals with chronic urticaria as the initial diagnosis revealed the presence of associated diseases in over half of the cases. The most prevalent diseases were infections and autoimmune diseases besides primary immunodeficiencies and blood diseases.

PMID: 27083494 [PubMed – as supplied by publisher]

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Cholecystitis and nephrotic syndrome complicating Epstein-Barr virus primary infection.

Paediatr Int Child Health. 2016 Jan 29;:1-4

Authors: Rodà D, Huici M, Ricart S, Vila J, Fortuny C, Alsina L

Abstract
Epstein-Barr virus (EBV) infection results in a spectrum of clinical manifestations. The host immune response to EBV plays a key role in the extent and degree of clinical features, which in children under 4 years of age are usually mild, non-specific and self-limiting. A 2-year-old boy in whom no known immune disorder could be found presented with acute acalculous cholecystitis, renal dysfunction with massive proteinuria, ascites, pleural effusion, minimal peripheral oedema and a severe systemic inflammatory response. Improvement occurred after initiation of corticosteroids and antiviral treatment with gancyclovir. In severely symptomatic or complicated EBV infection, a primary immunodeficiency must be suspected. If a primary immunodeficiency has been ruled out, the correct management of severe EBV infection in the immunocompetent host remains controversial.

PMID: 27077634 [PubMed – as supplied by publisher]

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