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Deficiency of Interleukin-1 Receptor-associated Kinase 4 Presenting as Fatal Pseudomonas aeruginosa Bacteremia in Two Siblings.

September 19, 2014 By Manish Butte

Deficiency of Interleukin-1 Receptor-associated Kinase 4 Presenting as Fatal Pseudomonas aeruginosa Bacteremia in Two Siblings.

Pediatr Infect Dis J. 2014 Sep 17;

Authors: Stergiopoulou T, Walsh TJ, Seghaye MC, Netea MG, Casanova JL, Moutschen M, Picard C

Abstract
Interleukin-1 receptor-associated kinase 4 (IRAK-4) deficiency is a primary immunodeficiency of innate immunity. This is the case of a previous healthy toddler and his sibling, who both died of fulminant sepsis due to Pseudomonas aeruginosa. Subsequent genetic analysis demonstrated IRAK-4 deficiency with compound heterozygous splice mutations. Fulminant fatal Pseudomonas aeruginosa sepsis may be the first manifestation of IRAK-4 deficiency.

PMID: 25232776 [PubMed – as supplied by publisher]

The use of databases in primary immunodeficiencies.

September 17, 2014 By Manish Butte

The use of databases in primary immunodeficiencies.

Curr Opin Allergy Clin Immunol. 2014 Sep 15;

Authors: Kindle G, Gathmann B, Grimbacher B

Abstract
PURPOSE OF REVIEW: We provide an overview on the latest developments in primary immunodeficiency registries worldwide, on the basis of the recent literature amended by some older references to achieve completeness.
RECENT FINDINGS: New primary immunodeficiency registries are emerging worldwide, although existing databases continue to thrive and provide valuable insights for clinicians and researchers.
SUMMARY: In the area of rare disease research, data on a meaningful number of patients can only be achieved via collaboration. Registries for primary immunodeficiency are organized on different geographic levels and appear in various technical forms. Some registries are operated within single departments or hospitals, whereas others collect data from a country in the form of a national registry. With modern information technology and networks, it has become feasible to easily extend documentation to the transnational level. Most patient registries cover similar but not identical sets of data, whereas some have a special focus on, for example, genetics or incorporate only data from patients who have undergone a specific form of treatment. This review shows the usefulness and power of international immunodeficiency registries, as well as possible hurdles and limitations.

PMID: 25225780 [PubMed – as supplied by publisher]

Long-term evaluation of a historical cohort of Iranian common variable immunodeficiency patients.

September 17, 2014 By Manish Butte

Long-term evaluation of a historical cohort of Iranian common variable immunodeficiency patients.

Expert Rev Clin Immunol. 2014 Oct;10(10):1405-1417

Authors: Aghamohammadi A, Abolhassani H, Latif A, Tabassomi F, Shokuhfar T, Torabi Sagvand B, Shahinpour S, Mirminachi B, Parvaneh N, Movahedi M, Gharagozlou M, Sherkat R, Amin R, Aleyasin S, Faridhosseini R, Jabbari-Azad F, Cheraghi T, Eslamian MH, Khalili A, Kalantari N, Shafiei A, Dabbaghzade A, Khayatzadeh A, Ebrahimi M, Razavinejad D, Bazregari S, Ebrahimi M, Ghaffari J, Bemanian MH, Behniafard N, Kashef S, Mohammadzadeh I, Hammarström L, Rezaei N

Abstract
Objectives: Common variable immune deficiency (CVID) is the most frequent form of symptomatic primary immunodeficiency disease, characterized by hypogammaglobulinemia, recurrent infections and increased predisposition to autoimmunity and malignancies. The aim of this study was to reconsider important points of previously performed studies on Iranian CVID patients diagnosed and followed from 1984 to 2013. Methods: Diagnosis was made using approved criteria including reductions of serum levels of immunoglobulins and exclusion of well-known single gene defects in individuals with an age >4 years and evidence of specific antibody deficiency. Results: Detailed information on demographic data, survival rates, clinical phenotypes, immunologic and genetic data and treatment of 173 patients are provided. The early onset presentation (74.5%) and rate of consanguineous marriage (61.2%) were considerably higher in our cohort. Our study revealed clinically related correlations regarding consanguinity, the population of naïve CD4(+) T cells and switched-memory B cells, cytokine levels and special genetic factors (including HLA and AID genes). Conclusion: Despite current efforts, more comprehensive studies are needed, especially for classification and investigation of the genetic background and prognostic factors for patients with CVID in order to better managment and followup of patinets.

PMID: 25225775 [PubMed – as supplied by publisher]

Evaluating for immunodeficiency in children with recurrent infection.

September 17, 2014 By Manish Butte

Evaluating for immunodeficiency in children with recurrent infection.

Aust Fam Physician. 2014 Sep;43(9):629-32

Authors: Lee AY, Gray PE

Abstract
BACKGROUND: Children have infections more frequently than adults. It may, therefore, be difficult to identify the rare child with immunodeficiency among the many who have recurrent infections but who have a normal immune system.
OBJECTIVE: The focus of this article will be on differentiating normal children from those with childhood primary immunodeficiency, through thorough clinical evaluation, and outlining some of the more important immunodeficiency diagnoses.
DISCUSSION: When investigating for immunodeficiency, the best available diagnostic tool is a thoughtful clinician with a good working knowledge of what is normal in terms of frequency and severity of childhood infection.

PMID: 25225649 [PubMed – in process]

A case of long-undiagnosed Common Primary Immunodeficiency in adulthood.

September 17, 2014 By Manish Butte

A case of long-undiagnosed Common Primary Immunodeficiency in adulthood.

Eur Ann Allergy Clin Immunol. 2014 Sep;46(5):184-8

Authors: Tirotta D, Durante V

Abstract
Common Variable Immunodeficiency (CVID) is one of the most common causes of Primary Immunodeficiency Disorders (PIDs) and of Primary Hypogammaglobulinemia in adulthood. Clinical features include variable combinations of infectious diseases, autoimmune diseases, lymphoproliferative disorders and gastrointestinal diseases. In this case report, delayed detection of the disease had a negative prognostic impact, despite prompt antibiotic and replacement therapy. The unfavourable prognosis was due to multi-organ failure (namely lungs, heart and liver) and to a number of chronic and acute infectious diseases.

PMID: 25224950 [PubMed – in process]

Diagnostic Immunization with Bacteriophage ΦX 174 in Patients with Common Variable Immunodeficiency/Hypogammaglobulinemia.

September 16, 2014 By Manish Butte

Diagnostic Immunization with Bacteriophage ΦX 174 in Patients with Common Variable Immunodeficiency/Hypogammaglobulinemia.

Front Immunol. 2014;5:410

Authors: Smith LL, Buckley R, Lugar P

Abstract
PURPOSE: Use of the T cell-dependent neoantigen bacteriophage ΦX 174 has been described since the 1960s as a method to assess specific antibody response in patients with primary immunodeficiencies. We reviewed a cohort of patients at Duke University Medical Center who received immunization with bacteriophage and report the clinical utility and safety of the immunization, as well as patient characteristics.
METHODS: A retrospective chart review was performed of all Duke Immunology Clinic patients (pediatric and adult) who received immunizations with bacteriophage, from 1976 to 2012. Subjects were selected for inclusion if their diagnosis at the time of bacteriophage was either presumed or confirmed common variable immunodeficiency (CVID), hypogammaglobulinemia, transient hypogammaglobulinemia, or antibody deficiency unspecified. Follow up post-immunization was also recorded.
RESULTS: One hundred twenty-six patients were identified, 36 adults and 90 pediatric patients. Diagnoses prior to bacteriophage were CVID (n = 100), hypogammaglobulinemia (n = 23), and antibody deficiency (n = 3). Post-immunization diagnoses were CVID (n = 65), hypogammaglobulinemia (n = 19), unknown (n = 23), no primary immune deficiency (n = 10), and other primary immunodeficiency (n = 9). Seventy-five patients had abnormal bacteriophage results, 37 were normal, and 14 were borderline. There were 257 recorded administrations of the immunization. Information was available on adverse reactions for 171 administrations. Fourteen immunizations were associated with minor adverse events. Nineteen patients stopped their immunoglobulin replacement therapy based on reported normal responses to immunization.
CONCLUSION: Bacteriophage ΦX 174 immunization is a safe, well-tolerated, and clinically useful method to assess antibody response in patients with suspected antibody-mediated immunodeficiencies, particularly those who are on immunoglobulin replacement therapy at the time of immunization.

PMID: 25221555 [PubMed]

2013 IDSA clinical practice guideline for vaccination of the immunocompromised host.

September 16, 2014 By Manish Butte

2013 IDSA clinical practice guideline for vaccination of the immunocompromised host.

Clin Infect Dis. 2014 Feb;58(3):309-18

Authors: Rubin LG, Levin MJ, Ljungman P, Davies EG, Avery R, Tomblyn M, Bousvaros A, Dhanireddy S, Sung L, Keyserling H, Kang I, Infectious Diseases Society of America

Abstract
An international panel of experts prepared an evidenced-based guideline for vaccination of immunocompromised adults and children. These guidelines are intended for use by primary care and subspecialty providers who care for immunocompromised patients. Evidence was often limited. Areas that warrant future investigation are highlighted.

PMID: 24421306 [PubMed – indexed for MEDLINE]

2013 IDSA clinical practice guideline for vaccination of the immunocompromised host.

September 16, 2014 By Manish Butte

2013 IDSA clinical practice guideline for vaccination of the immunocompromised host.

Clin Infect Dis. 2014 Feb;58(3):e44-100

Authors: Rubin LG, Levin MJ, Ljungman P, Davies EG, Avery R, Tomblyn M, Bousvaros A, Dhanireddy S, Sung L, Keyserling H, Kang I, Infectious Diseases Society of America

PMID: 24311479 [PubMed – indexed for MEDLINE]

Pineal Germinoma in a Child with Interferon-γ Receptor 1 Deficiency. Case Report and Literature Review.

September 14, 2014 By Manish Butte

Pineal Germinoma in a Child with Interferon-γ Receptor 1 Deficiency. Case Report and Literature Review.

J Clin Immunol. 2014 Sep 14;

Authors: Taramasso L, Boisson-Dupuis S, Garrè ML, Bondi E, Cama A, Nozza P, Morana G, Casanova JL, Marazzi MG

Abstract
Interferon-γ receptor 1 (IFN-γR1) deficiency is one of the primary immunodeficiencies conferring Mendelian Susceptibility to Mycobacterial Disease (MSMD). Some cases of neoplasms have been recently reported in patients with MSMD, underlying the already known link between immunodeficiency and carcinogenesis. We report the first case of intracranial tumour, i.e. pineal germinoma, in a 11-year-old patient with complete IFN-γR1 deficiency. The first clinical presentation of the genetic immunodeficiency dates back to when the child was aged 2 y and 10 mo, when he presented a multi-focal osteomyelitis caused by Mycobacterium scrofulaceum. The diagnosis of IFN-γR1 deficiency (523delT/523delT in IFNGR1 gene) was subsequently made. The child responded to antibiotic therapy and remained in stable clinical condition until the age of 11 years, when he started complaining of frontal, chronic headache. MRI revealed a solid pineal region mass lesion measuring 20 × 29 × 36 mm. Histological findings revealed a diagnosis of pineal germinoma. The patient received chemotherapy followed by local whole ventricular irradiation with boost on pineal site, experiencing complete remission, and to date he is tumor-free at four years follow-up. Four other cases of tumors have been reported in patients affected by MSMD in our knowledge: a case of Kaposi sarcoma, a case of B-cell lymphoma, a case of cutaneous squamous cell carcinoma and a case of oesophageal squamous cell carcinoma. In conclusion, in patients with MSMD, not only the surveillance of infectious diseases, but also that of tumors is important.

PMID: 25216720 [PubMed – as supplied by publisher]

Clinical Features and Genetic Analysis of 20 Chinese Patients with X-Linked Hyper-IgM Syndrome.

September 13, 2014 By Manish Butte

Clinical Features and Genetic Analysis of 20 Chinese Patients with X-Linked Hyper-IgM Syndrome.

J Immunol Res. 2014;2014:683160

Authors: Wang LL, Zhou W, Zhao W, Tian ZQ, Wang WF, Wang XF, Chen TX

Abstract
X-linked hyper-IgM syndrome (XHIGM) is one type of primary immunodeficiency diseases, resulting from defects in the CD40 ligand/CD40 signaling pathways. We retrospectively analyzed the clinical and molecular features of 20 Chinese patients diagnosed and followed up in hospitals affiliated to Shanghai Jiao Tong University School of Medicine from 1999 to 2013. The median onset age of these patients was 8.5 months (range: 20 days-21 months). Half of them had positive family histories, with a shorter diagnosis lag. The most common symptoms were recurrent sinopulmonary infections (18 patients, 90%), neutropenia (14 patients, 70%), oral ulcer (13 patients, 65%), and protracted diarrhea (13 patients, 65%). Six patients had BCGitis. Six patients received hematopoietic stem cell transplantations and four of them had immune reconstructions and clinical remissions. Eighteen unique mutations in CD40L gene were identified in these 20 patients from 19 unrelated families, with 12 novel mutations. We compared with reported mutation results and used bioinformatics software to predict the effects of mutations on the target protein. These mutations reflected the heterogeneity of CD40L gene and expanded our understanding of XHIGM.

PMID: 25215306 [PubMed – in process]