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Persistent Immune Activation in CVID and the Role of IVIg in Its Suppression.

Front Immunol. 2014;5:637

Authors: Paquin-Proulx D, Sandberg JK

Abstract
Common variable immunodeficiency (CVID) is one of the most common and clinically important primary immune deficiencies. CVID patients have poor humoral immunity, resulting in recurrent infections of the gastrointestinal and upper respiratory tracts, as well as increased incidence of some forms of cancers and autoimmune diseases. The treatment for CVID is IgG replacement, often given as intravenous immunoglobulins (IVIg). IVIg consists of monomeric IgG purified from pooled plasma from healthy donors and is used to treat an increasing number of conditions including autoimmune diseases. In the case of CVID, IVIg has mainly been seen as reconstitution therapy, providing patients with pathogen-specific antibodies. Recent evidence shows that IVIg has diverse effects on the immune system of CVID patients, and one important component is that IVIg alleviates the state of chronic immune activation. In this review, we will discuss causes and consequences of persistent immune activation in CVID, possible underlying mechanisms for how IVIg treatment reduces immune activation, and implications for our understanding of primary as well as acquired immune deficiencies.

PMID: 25566250 [PubMed – as supplied by publisher]

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Primary Cutaneous Cryptococcosis in an Eight-year-old Immunocompetent Child: How to Treat?

Klin Padiatr. 2015 Jan;227(1):41-44

Authors: Lenz D, Held J, Goerke S, Wagner D, Tintelnot K, Henneke P, Hufnagel M

Abstract
Here we report on a case of primary cryptococcal skin infection in an immunocompetent 8-year-old boy. The infection first manifested itself as a subcutaneous abscess around the proximal joint of his right thumb after a minor injury from contact with a thorny shrub. After surgical incision and drainage was performed, Cryptococcus neoformans var. neoformans was the only pathogen cultured from the lesion. An agglutination test for the capsular antigen in serum displayed negative results and the immunological work-up revealed no underlying immunodeficiency. A “watch and wait” strategy – one without systemic antifungal treatment – was adopted and this resulted in uneventful healing. In summary, primary cryptococcal skin infections in immunocompetent hosts may be managed successfully by surgical treatment in combination with careful clinical follow-up. This approach may help avoid unnecessary antimicrobial treatments.

PMID: 25565197 [PubMed – as supplied by publisher]

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CADM1 expression and stepwise downregulation of CD7 are closely associated with clonal expansion of HTLV-I-infected cells in adult T-cell leukemia/lymphoma.

Clin Cancer Res. 2014 Jun 1;20(11):2851-61

Authors: Kobayashi S, Nakano K, Watanabe E, Ishigaki T, Ohno N, Yuji K, Oyaizu N, Asanuma S, Yamagishi M, Yamochi T, Watanabe N, Tojo A, Watanabe T, Uchimaru K

Abstract
PURPOSE: Cell adhesion molecule 1 (CADM1), initially identified as a tumor suppressor gene, has recently been reported to be ectopically expressed in primary adult T-cell leukemia-lymphoma (ATL) cells. We incorporated CADM1 into flow-cytometric analysis to reveal oncogenic mechanisms in human T-cell lymphotrophic virus type I (HTLV-I) infection by purifying cells from the intermediate stages of ATL development.
EXPERIMENTAL DESIGN: We isolated CADM1- and CD7-expressing peripheral blood mononuclear cells of asymptomatic carriers and ATLs using multicolor flow cytometry. Fluorescence-activated cell sorted (FACS) subpopulations were subjected to clonal expansion and gene expression analysis.
RESULTS: HTLV-I-infected cells were efficiently enriched in CADM1(+) subpopulations (D, CADM1(pos)CD7(dim) and N, CADM1(pos)CD7(neg)). Clonally expanding cells were detected exclusively in these subpopulations in asymptomatic carriers with high proviral load, suggesting that the appearance of D and N could be a surrogate marker of progression from asymptomatic carrier to early ATL. Further disease progression was accompanied by an increase in N with a reciprocal decrease in D, indicating clonal evolution from D to N. The gene expression profiles of D and N in asymptomatic carriers showed similarities to those of indolent ATLs, suggesting that these subpopulations represent premalignant cells. This is further supported by the molecular hallmarks of ATL, that is, drastic downregulation of miR-31 and upregulation of abnormal Helios transcripts.
CONCLUSION: The CADM1 versus CD7 plot accurately reflects disease progression in HTLV-I infection, and CADM1(+) cells with downregulated CD7 in asymptomatic carriers have common properties with those in indolent ATLs.

PMID: 24727323 [PubMed – indexed for MEDLINE]

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A 15-year old girl with asthma and lower lobe bronchiectasis.

Allergy Asthma Proc. 2015 Jan;36(1):82-86

Authors: Ricketti PA, Unkle DW, King KA, Cleri DJ, Ricketti AJ

Abstract
Wet cough, wheeze, and sputum in an adolescent with evidence for bronchiectasis is an uncommon presentation. The differential diagnosis includes cystic fibrosis (CF), immunodeficiency disorders, complement deficiency, allergic bronchopulmonary aspergillosis, alpha-1 antitrypsin disease, repeated aspiration pneumonia, foreign body, bronchial carcinoid, unresolved right middle lobe pneumonia, and primary ciliary dyskinesia (PCD). The likely diagnosis proceeds from the more to less common in patients with these symptoms. The location of disease on computed tomography scanning, nasal and bronchial exhaled nitric oxide, identification of ultrastructural defects on electron microscopy, and specific genetic mutation help separate CF and PCD. Although differentiating these conditions is vital, the chronic management of the bronchiectasis usually includes clearance mechanisms, bronchodilators, regular exercise, appropriate vaccinations, and judicious antibiotics for airway infections.

PMID: 25562561 [PubMed – as supplied by publisher]

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Necrotizing and sarcoidal granulomas in the skin and synovial membrane, associated with common variable immunodeficiency.

Clin Exp Dermatol. 2014 Dec 31;

Authors: Plana Pla A, Bassas-Vila J, Roure S, Ferrándiz C

Abstract
Common variable immunodeficiency (CVID) is a primary immunodeficiency characterized by hypogammaglobulinaemia, T-cell abnormalities and recurrent bacterial infections. Patients with CVID can present granulomatous lesions on both the skin and other organs. When these lesions are the first sign of the disease, the diagnosis can be very challenging. We report the case of a patient with undiagnosed CVID, who presented with necrotizing and sarcoidal granulomas on the skin and synovial membrane as the first appearance of immunodeficiency.

PMID: 25557739 [PubMed – as supplied by publisher]

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Important differences in the diagnostic spectrum of primary immunodeficiency in adults versus children.

Expert Rev Clin Immunol. 2015 Jan 5;:1-14

Authors: Abolhassani H, Rezaei N, Mohammadinejad P, Mirminachi B, Hammarstrom L, Aghamohammadi A

Abstract
Primary immunodeficiency disorders (PIDs) constitute a heterogeneous group of genetic disorders caused by defects in immunity, leading to recurrent infections, autoimmunity, lymphoproliferation and malignancies. Early diagnosis of PIDs is crucial for improving the quality of life in patients with PIDs while a delay in diagnosis, or inadequate treatment, results in an increased mortality and morbidity in affected individuals. Although most cases of PIDs present in children with recurrent and/or severe acute infections, some of the primary immune disorders are diagnosed during adulthood. Some common clues, both in children and adults, help physicians to diagnose PIDs; however, there are some specific clues to the diagnosis of PIDs for each group. This article reviews the important differences in the diagnostic spectrum of PIDs in adults versus children.

PMID: 25556968 [PubMed – as supplied by publisher]

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Antibiotic prophylaxis in primary immune deficiency disorders.

J Allergy Clin Immunol Pract. 2013 Nov-Dec;1(6):573-82

Authors: Kuruvilla M, de la Morena MT

Abstract
Long-term prophylactic antibiotics are being widely implemented as primary or adjunctive therapy in primary immune deficiencies. This practice has transformed clinical outcomes in the setting of chronic granulomatous disease, complement deficiencies, Mendelian susceptibility to mycobacterial disease, Wiskott-Aldrich syndrome, hyper-IgE syndrome, Toll signaling defects, and prevented Pneumocystis in patients with T-cell deficiencies. Yet, controlled trials are few in the context of primary antibody deficiency syndromes, and most of this practice has been extrapolated from data in patients who are immune competent and with recurrent acute otitis media, chronic rhinosinusitis, cystic fibrosis, and bronchiectasis. The paucity of guidelines on the subject is reflected in recent surveys among practicing immunologists that highlight differences of habit regarding this treatment. Such discrepancies reinforce the lack of standard protocols on the subject. This review will provide evidence for the use of antibiotic prophylaxis in various primary immune deficiency populations, especially highlighting the role antibiotic prophylaxis in primary antibody deficiency syndromes. We also discussed the relationship of long-term antibiotic use and the prevalence of resistant pathogens. Overall, examination of available data on the use of prophylactic antibiotics in antibody deficiency syndromes merit future investigation in well-designed multicenter prospective trials because this population has few other management options.

PMID: 24565703 [PubMed – indexed for MEDLINE]

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Distribution of primary immunodeficiency disorders diagnosed in a tertiary referral center, tehran, iran (2006-2013).

Iran J Immunol. 2014 Dec;11(4):282-91

Authors: Mohammadinejad P, Mirminachi B, Sadeghi B, Movahedi M, Gharagozlou M, Mohammadi J, Abolhassani H, Rezaei N, Aghamohammadi A

Abstract
BACKGROUND: Primary immunodeficiency disorders (PID) are a group of hereditary disorders characterized by an increased susceptibility to severe and recurrent infections, autoimmunity, lymphoproliferative disorders, and malignancy.
OBJECTIVE: To evaluate the demographic and clinical data of PID patients diagnosed in a referral pediatric hospital.
METHOD: All PID cases with a confirmed diagnosis, according to the criteria of International Union of Immunological Societies, who were referred to the Children’s Medical Center in Tehran, Iran, between March 2006 and March 2013 were enrolled in this retrospective cohort study.
RESULTS: Three-hundred and seven PID patients were investigated. Predominantly antibody deficiencies were the most common group of PID observed in 118 cases (38.4%), followed by the well-defined syndromes with immunodeficiency in 52 (16.9%), congenital defects of phagocyte in 45 (14.7%), combined immunodeficiencies in 36 (11.7%), autoinflammatory disorders in 34 (11.4%), immune dysregulation in 11 (3.6%), complement deficiencies in 7 (2.3%), and defects in innate immunity in 3 (1%). Selective IgA deficiency was the most prevalent disorder which affected 46 individuals (14.9%). The median diagnostic delay was 15 months.
CONCLUSION: Increased awareness and availability of diagnostic tests could result in the better recognition of more undiagnosed PID cases and a decrease in diagnostic delay.

PMID: 25549596 [PubMed – in process]

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The correlation between NK cell and liver function in patients with primary hepatocellular carcinoma.

Gut Liver. 2014 May;8(3):298-305

Authors: Sha WH, Zeng XH, Min L

Abstract
BACKGROUND/AIMS: This study aimed to detect the expression of natural killer (NK) cell receptor natural killer group 2D (NKG2D) in the peripheral blood of patients with primary hepatocellular carcinoma and to discuss the correlation between NK cell cytotoxicity and liver function.
METHODS: The number of NK cells and the expression of NK cell receptor NKG2D in peripheral blood were determined by flow cytometry in patients with primary hepatocellular carcinoma, hepatitis B cirrhosis, chronic hepatitis B, and healthy controls.
RESULTS: When compared with patients in the healthy and the chronic hepatitis B groups, the primary hepatocellular carcinoma group showed significant decreases in all parameters, including the cytotoxicity of NK cells on K562 cells, expression rate of NKG2D in NK cells, number of NKG2D(+) NK cells, expression level of NKG2D, and number of NK cells (p<0.05). The activity of NK cells showed a positive correlation, whereas the Child-Pugh scores in the primary hepatocellular carcinoma and the hepatitis B cirrhosis groups showed a negative correlation with all parameters detected above.
CONCLUSIONS: The decrease of NK cell activity in patients with primary hepatocellular carcinoma is closely related to their lower expression of NKG2D. Liver function affects the expression of NKG2D and the activity of NK cells.

PMID: 24827627 [PubMed – indexed for MEDLINE]

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7(th) International Immunoglobulin Conference: Poster Presentations.

Clin Exp Immunol. 2014 Dec;178 Suppl S1:162

Authors: Warnatz K, Ballow M, Stangel M, Bril V

Abstract
The pan-European survey provides useful information on the accessibility and trends of intravenous and subcutaneous immunoglobulin (IVIg/SCIg) therapy, which is used to treat primary immunodeficiency disorders (PIDs). Although immunoglobulin (Ig) therapy is the first-line treatment for PIDs, the mechanisms of action of Ig therapy may differ according to the condition it is used to treat. Moreover, intriguing presentations suggest that further investigation is required to understand more clearly both the haematological and immunoregulatory effects of therapeutic immunoglobulin. This can ultimately provide more information on optimizing Ig therapy efficacy, and establish whether individualized dosing regimens for patients will be conducive to better clinical outcomes. In addition to treating autoimmune and inflammatory conditions, there is evidence to suggest that immunoglobulins can potentially play a role in transplantation, which warrants further investigation for future use.

PMID: 25546805 [PubMed – as supplied by publisher]

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