Stanford Alliance for Primary Immunodeficiency

Stanford University

You are here: Home / Archives for Manish Butte

Manish Butte

Common Variable Immunodeficiency.

By

Common Variable Immunodeficiency.

Indian J Pediatr. 2016 Feb 12;

Authors: Saikia B, Gupta S

Abstract
Common variable immunodeficiency (CVID) is the most common primary immunodeficiency of young adolescents and adults which also affects the children. The disease remains largely under-diagnosed in India and Southeast Asian countries. Although in majority of cases it is sporadic, disease may be inherited in a autosomal recessive pattern and rarely, in autosomal dominant pattern. Patients, in addition to frequent sino-pulmonary infections, are also susceptible to various autoimmune diseases and malignancy, predominantly lymphoma and leukemia. Other characteristic lesions include lymphocytic and granulomatous interstitial lung disease, and nodular lymphoid hyperplasia of gut. Diagnosis requires reduced levels of atleast two immunoglobulin isotypes: IgG with IgA and/or IgM and impaired specific antibody response to vaccines. A number of gene mutations have been described in CVID; however, these genetic alterations account for less than 20 % of cases of CVID. Flow cytometry aptly demonstrates a disturbed B cell homeostasis with reduced or absent memory B cells and increased CD21(low) B cells and transitional B cell populations. Approximately one-third of patients with CVID also display T cell functional defects. Immunoglobulin therapy remains the mainstay of treatment. Immunologists and other clinicians in India and other South East Asian countries need to be aware of CVID so that early diagnosis can be made, as currently, majority of these patients still go undiagnosed.

PMID: 26868026 [PubMed – as supplied by publisher]

Powered by WPeMatico

Intrafamily and Interfamilial Phenotype Variation and Immature Immunity in Patients With Netherton Syndrome and Finnish SPINK5 Founder Mutation.

By

Related Articles

Intrafamily and Interfamilial Phenotype Variation and Immature Immunity in Patients With Netherton Syndrome and Finnish SPINK5 Founder Mutation.

JAMA Dermatol. 2016 Feb 10;

Authors: Hannula-Jouppi K, Laasanen SL, Ilander M, Furio L, Tuomiranta M, Marttila R, Jeskanen L, Häyry V, Kanerva M, Kivirikko S, Tuomi ML, Heikkilä H, Mustjoki S, Hovnanian A, Ranki A

Abstract
Importance: Netherton syndrome (NS) is a rare and severe genodermatosis caused by SPINK5 mutations leading to the loss of lymphoepithelial Kazal-type-related inhibitor (LEKTI). Netherton syndrome is characterized by neonatal scaling erythroderma, a bamboolike hair defect, a substantial skin barrier defect, and a profound atopic diathesis. Netherton syndrome has been proposed to be a primary immunodeficiency syndrome because of the high frequency of infections. The precise mechanisms underlying the disease are not fully understood.
Objective: To study the association of the SPINK5 mutation with the NS phenotype and the extent of immunologic deficiencies in NS.
Design, Setting, and Participants: Relevant tissue samples and follow-up data from 11 patients with NS from 7 families, including 3 multiplex families, were collected, constituting all known patients with NS in Finland. Another patient with NS from a neighboring country was included. Data were collected from August 10, 2011, to February 20, 2015. SPINK5 mutations were sequenced, and thorough clinical evaluation and histopathologic and immunohistochemical evaluations of skin samples were performed. The function of natural killer cells, lymphocyte phenotype, and serum immunoglobulin subclass levels were evaluated. Data analysis was conducted from October 19, 2011, to February 20, 2015.
Main Outcomes and Measures: The nature of SPINK5 mutations and their correlation with phenotypes in Finnish patients with NS, intrafamilial phenotype variations, and the type of immunologic defects in NS were evaluated.
Results: Among the 11 Finnish patients with NS (8 male [73%]; 3 female [27%]; mean [SD] age, 30.1 [9.1] years), a Finnish founder mutation c.652C>T (p.Arg218*) in SPINK5 was identified in 10 patients from 6 families who all originated from the same region. Eight patients were homozygotes for this mutation and 2 siblings were compound heterozygotes with a splice site mutation c.1220 + 1G>C (IVS13 + 1 G>C). Phenotypes were comparable, but some intrafamilial and interfamilial variations were noted. Compound heterozygous patients had a milder phenotype and showed residual LEKTI expression. A previously unreported c.1772delT (p.Leu591Glnfs124*) mutation was found in 1 patient with a phenotype similar to the patients homozygous for the founder mutation. The patient from the neighboring country had a distinct phenotype and different mutations. Immunologically, natural killer cells had an immature phenotype and impaired cytotoxicity and degranulation, levels of memory B cells were reduced, and serum IgG4 levels were elevated. Intravenous immunoglobulin treatment has been beneficial in 1 patient with NS.
Conclusions and Relevance: This report discloses a prevalent SPINK5 founder mutation in Finland and illustrates NS phenotype variability. Our results also point to a possible role of immature immunity in the frequent infections seen in NS.

PMID: 26865388 [PubMed – as supplied by publisher]

Powered by WPeMatico

Application of Flow Cytometry in the Evaluation of Primary Immunodeficiencies.

By

Related Articles

Application of Flow Cytometry in the Evaluation of Primary Immunodeficiencies.

Indian J Pediatr. 2016 Feb 11;

Authors: Fleisher TA, Madkaikar M, Rosenzweig SD

Abstract
Primary immunodeficiency disorders (PIDDs) are a heterogeneous group of inherited disorders of the immune system. Currently more than 250 different PIDDs with a known genetic defect have been recognized. The diagnosis of many of these disorders is supported strongly by a wide variety of flow cytometry applications. Flow cytometry offers a rapid and sensitive tool for diagnosis and classification of PIDDs. It is applicable in the initial workup and subsequent management of several primary immunodeficiency diseases. As our understanding of the pathogenesis and management of these diseases increases, the majority of these tests can be easily established in the diagnostic laboratory. Thus, the focus of this article is on the application of flow cytometry in the diagnosis and/or evaluation of PIDDs.

PMID: 26865168 [PubMed – as supplied by publisher]

Powered by WPeMatico

Hodgkin lymphoma risk following infectious and chronic inflammatory diseases: a large population-based case-control study from Sweden.

By

Related Articles

Hodgkin lymphoma risk following infectious and chronic inflammatory diseases: a large population-based case-control study from Sweden.

Int J Hematol. 2015 Jun;101(6):563-8

Authors: Kristinsson SY, Gao Y, Björkholm M, Lund SH, Sjöberg J, Caporaso N, Goldin LR, Landgren O

Abstract
Patients with Hodgkin lymphoma (HL) have a well-characterized immune deficiency of T cell function, originally identified by increased susceptibility to certain infections. Epidemiological evidence has long pointed to infectious etiologies in younger HL patients. With the aim of expanding our knowledge on the potential role of pre-existing immune deficiency in HL and an infectious/inflammatory etiology, we conducted a comprehensive population-based case-control study in HL patients diagnosed in Sweden in the period 1965-2004, and their matched controls. In a large population-based study including 7,414 HL patients and 29,240 matched controls, we evaluated the subsequent risk of HL in relation to a broad range of infectious and inflammatory conditions, using unconditional logistic regression. A previous history of any reported infection was associated with an 11 % increased risk of HL (P < 0.05). More specifically, we found sinusitis (odds ratio = 1.81; 95 % confidence interval = 1.06-3.07), tuberculosis (1.76; 1.01-3.07), encephalitis (7.88; 1.97-31.5), and herpes zoster (2.20; 1.11-4.35) to be associated with excess HL risk. A personal prior history of chronic inflammatory condition was not associated with an increased risk of HL (0.94; 0.71-1.14). Our results suggest that underlying immune deficiency is a primary phenomenon in HL. Alternatively, certain infectious agents may be potential HL triggers.

PMID: 25758095 [PubMed – indexed for MEDLINE]

Powered by WPeMatico

The effects of prenatal genetic analysis on fetuses born to carrier mothers with primary immunodeficiency diseases.

By

The effects of prenatal genetic analysis on fetuses born to carrier mothers with primary immunodeficiency diseases.

Ann Med. 2016 Feb 8;:1-8

Authors: Lee WI, Huang JL, Yeh KW, Cheng PJ, Jaing TH, Lin SJ, Chen LC, Ou LS, Yao TC

Abstract
Objective Prenatal genetic analysis in primary immunodeficiency diseases (PIDs) can decrease morbidity and mortality. Methods We compared the postnatal prognoses of index cases and their subsequent sibling-fetuses using prenatal genetic analysis. Results From 2007 to 2014, 14 sibling-fetuses receiving a prenatal diagnosis born to four mothers with WAS, three with X-CGD, and one each with IPEX, XLA and severe combined immunodeficiency [RAG2-SCID] were recruited. There were six affected, two carriers, and six wild types. Among the six affected, four [3X-CGD and 1RAG2-SCID] were terminated and two [1WAS and 1X-CGD] with early prophylactics underwent successful hematopoietic stem cell transplantation (HSCT) without infection. In the 12 index cases with a postnatal diagnosis, eight died (five due to infections and one each due to refractory bleeding, severe diarrhea, and post-transplant pneumothorax), two X-CGD underwent reconstituted HSCT after recurrent life-threatening infections, one WAS developed malignancy, and another WAS developed autoimmune disorders despite the administration of prophylactics and regular immunoglobulin infusion. Conclusion Instead of recurrent life-threatening infections leading to mortality in the postnatal diagnosis group, the severe PIDs who received early prophylactics were cured by HSCT, and all of mortality were terminations in the prenatal diagnosis group. Further large-scale studies are needed to validate this beneficial effect. Key message Prenatal genetic analysis in fetuses born to PIDs carrier mothers allows for the affected fetuses to receive optimal management including prophylactics against infections and HSCT if indicated. Patients with PIDs diagnosed postnatally who are prone to severe infections have higher rates of morbidity and mortality than their subsequent siblings who have a prenatal genetic diagnosis.

PMID: 26856578 [PubMed – as supplied by publisher]

Powered by WPeMatico

Causes of mortality in farmed mink in the Intermountain West, North America.

By

Related Articles

Causes of mortality in farmed mink in the Intermountain West, North America.

J Vet Diagn Invest. 2015 Jul;27(4):470-5

Authors: Wilson DJ, Baldwin TJ, Whitehouse CH, Hullinger G

Abstract
The primary causes of mortality were identified in postmortem examination of 339 (90.9%) of 373 farmed mink (Neovison vison; syn. Mustela vison) from January 2009 through June 2014 at the Utah Veterinary Diagnostic Laboratory (Logan, Utah). Mink were raised under farm conditions in the Intermountain West in North America, except for 1 submission of mink from Wisconsin. In the 339 mink where cause(s) of death were established, 311 (91.7%) died from a single disease or condition, whereas 28 (8.3%) had 2 diseases or conditions contributing to death. Where cause(s) of death were evident, 11 diseases accounted for 321 (94.7%) of the diagnoses: bacterial pneumonia (67, 18.8%), Aleutian mink disease (61, 17.7%), mink viral enteritis (56, 16.2%), hepatic lipidosis (28, 8.1%), nutritional myopathy (24, 7%), bacterial enterocolitis (17, 4.9%), bacterial septicemia (16, 4.6%), starvation (15, 4.3%), epizootic catarrhal gastroenteritis of mink (14, 4.1%), pancreatitis (13, 3.8%), and bacterial metritis (10, 2.9%). In 34 (9.1%) animals, a cause of death was not evident. In an additional 16 (4.3%) of the mink, botulism was suspected from clinical history but could not be confirmed by laboratory testing. Control measures for the most common causes of death in farmed mink include testing and removal of positive animals (Aleutian mink disease), vaccination (Pseudomonas aeruginosa pneumonia, mink viral enteritis), avoidance of obesity in mink (hepatic lipidosis), and environmental management, including maintaining clean water cups, floors, feed troughs, cages, feed silos, feed truck tires, workers’ shoes, dining areas for farm personnel, leather mink handling gloves, street clothes, and coveralls.

PMID: 26077544 [PubMed – indexed for MEDLINE]

Powered by WPeMatico