Research

[Radiographic changes in children with primary immunodeficiency].

Rev Alerg Mex. 2015 Jul-Sep;62(3):211-218

Authors: González-Uribe V, Pietropaolo-Cienfuegos DR, Del Río-Navarro BE, Del Río-Chivardi JM, Sienra-Monge JJ

Abstract
BACKGROUND: Although we have epidemiological information on primary immunodeficiencies (PID), the available information is meager in Mexico.
OBJECTIVE: To provide epidemiological information on the delay in the diagnosis of PID and its correlation to chronic lung damage.
MATERIAL AND METHOD: A retrospective, analytical study was done in patients 0-18 year old age diagnosed with PID for 11 years at the HIMFG (Hospital Infantil de Mexico Federico Gomez). The variables studied were: age at symptom onset, age at diagnosis, time from onset of symptoms to diagnosis, number of previous pneumonias and studies with radiographic chronic lung damage data.
RESULTS: 48 patients were obtained after meeting inclusion criteria; 33 showed lung damage at diagnosis, antibody deficiency being the most affected group. Relating age of onset of symptoms and the time difference of the onset of symptoms to diagnosis showed a strong correlation (p < 0.001, Rho > 0.80). A moderate correlation between the observed time difference vs number of pneumonias (p=0.005, Rho=0.495) and correlation between number of pneumonia and lung damage was highly significant (p <0.001, Rho=0.704).
CONCLUSION: A strong relationship between the elapsed time from onset of symptoms and the number of pneumonia with lung injury time was found. So, the recurrent pneumonia (> 2) must make suspect the diagnosis of PID, as recommended in the literature.

PMID: 26239331 [PubMed – as supplied by publisher]

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[EFFICIENCY OF COMBINATION OF ROFLUMILAST AND QUERCETIN FOR CORRECTION OXYGEN- INDEPENDENT MECHANISMS AND PHAGOCYTIC ACTIVITY OF MACROPHAGE CELLS OF PATIENTS WITH ACUTE EXACERBATION OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE WHEN COMBINED WITH CORONARY HEART DISEASE].

Lik Sprava. 2015 Jan-Mar;(1-2):67-76

Authors: Gerych P, Yatsyshyn R

Abstract
Studied oxygen independent reaction and phagocytic activity of macrophage cells of patients with chronic obstructive pulmonary disease (COPD) II-III stage when combined with coronary heart disease (CHD). The increasing oxygen independent reactions monocytes and neutrophils and a decrease of the parameters that characterize the functional state of phagocytic cells, indicating a decrease in the functional capacity of macrophage phagocytic system (MPS) in patients with acute exacerbation of COPD, which runs as its own or in combination with stable coronary heart disease angina I-II. FC. Severity immunodeficiency state in terms of cellular component of nonspecific immunity in patients with acute exacerbation of COPD II-III stage in conjunction with the accompanying CHD increases with the progression of heart failure. Inclusion of basic therapy of COPD exacerbation and standard treatment of coronary artery disease and drug combinations Roflumilastand quercetin causes normalization of phagocytic indices MFS, indicating improved immune status and improves myocardial perfusion in terms of daily ECG monitoring.

PMID: 26118031 [PubMed – indexed for MEDLINE]

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Severe combined immunodeficiency-an update.

Ann N Y Acad Sci. 2015 Jul 31;

Authors: Cirillo E, Giardino G, Gallo V, D’Assante R, Grasso F, Romano R, Lillo CD, Galasso G, Pignata C

Abstract
Severe combined immunodeficiencies (SCIDs) are a group of inherited disorders responsible for severe dysfunctions of the immune system. These diseases are life-threatening when the diagnosis is made too late; they are the most severe forms of primary immunodeficiency. SCID patients often die during the first two years of life if appropriate treatments to reconstitute their immune system are not undertaken. Conventionally, SCIDs are classified according either to the main pathway affected by the molecular defect or on the basis of the specific immunologic phenotype that reflects the stage where the blockage occurs during the differentiation process. However, during the last few years many new causative gene alterations have been associated with unusual clinical and immunological phenotypes. Many of these novel forms of SCID also show extra-hematopoietic alterations, leading to complex phenotypes characterized by a functional impairment of several organs, which may lead to a considerable delay in the diagnosis. Here we review the biological and clinical features of SCIDs paying particular attention to the most recently identified forms and to their unusual or extra-immunological clinical features.

PMID: 26235889 [PubMed – as supplied by publisher]

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[Chronic granulomatous disease: three cases with different presentations].

Rev Chil Pediatr. 2015 Mar-Apr;86(2):112-6

Authors: D GE, B KB, P VP, R XN, L AQ

Abstract
INTRODUCTION: Chronic granulomatous disease (CGD) is a rare form of primary immunodeficiency disease, characterized by an abnormal susceptibility to bacterial and fungal infections, and it is caused by a deficit in the phagocyte nicotinamide adenine dinucleotide phosphate oxidase complex (NADPH), resulting in the inability to generate reactive oxygen species that destroy microorganisms. The diagnosis is based on clinical characteristics and analysis of phagocytes, and later confirmed by molecular studies. Its management should consider antimicrobial prophylaxis, a search for infections and aggressive management of these.
OBJECTIVE: To describe three cases of CGD emphasizing their forms of presentation and to conduct a review of the condition.
CASE REPORTS: Three case reports, two of them first cousins, are presented. Molecular diagnosis was reached in one of the cases. Recurrent infections, abscesses, adenitis, granulomas and complications are identified to facilitate the suspected diagnosis of CGD, bearing in mind the importance of early diagnosis and genetic counseling.
CONCLUSIONS: EGC is a rare congenital primary immunodeficiency disorder, mostly with X-linked inheritance, autosomal recessive form, and a specific presentation form. Its diagnosis should be timely to avoid complications. Prophylaxis and aggressive treatment of infections should be performed, as well as genetic counseling.

PMID: 26235691 [PubMed – in process]

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Severe and Rapid Progression in Very Early-Onset Chronic Granulomatous Disease-Associated Colitis.

J Clin Immunol. 2015 Aug 2;

Authors: Kawai T, Arai K, Harayama S, Nakazawa Y, Goto F, Maekawa T, Tamura E, Uchiyama T, Onodera M

Abstract
PURPOSE: Chronic granulomatous disease (CGD) is a primary immunodeficiency disease that leads to recurrent infection and hyper-inflammation, occasionally represented by CGD-associated colitis (CGD colitis). Although clinical symptoms of CGD colitis mimic those of ulcerative colitis (UC), there is no reliable standard measurement of disease activity or standard therapeutic strategy for CGD colitis. Here, we examined the clinical manifestation of CGD colitis based on severity using a noninvasive measure of disease activity, the Pediatric Ulcerative Colitis Activity Index (PUCAI), which has been validated and widely used for pediatric UC.
METHODS: Sixteen of 35 CGD patients, who were diagnosed with CGD colitis based on colonoscopic and histological findings, were examined using the PUCAI. Both the PUCAI and the physician global assessment (PGA) tool were retrospectively scored by reviewing medical records.
RESULTS: Disease activity defined by PUCAI was correlated with PGA, and increased at diagnosis of CGD colitis, especially in patients who were younger than 6 years of age (very early-onset CGD colitis: VEO-CGD colitis) when diagnosed with CGD colitis. All severe patients had a more progressive form of VEO-CGD colitis. Unlike mild and moderate patients, severe patients required multidrug therapy of corticosteroids and immunomodulator/immunosuppressants, and some were eventually treated with hematopoietic stem cell transplantation.
CONCLUSIONS: Although the validation of PUCAI in CGD colitis should be considered for future use, our results indicate that noninvasive measures could be effective to measure disease activity and help to determine suitable treatment for CGD colitis. In patients with VEO-CGD colitis, multidrug therapy would need to be considered at an early stage on the basis of disease activity.

PMID: 26233238 [PubMed – as supplied by publisher]

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Antibiotic resistance in patients with primary immunodeficiency disorders versus immunocompetent patients.

Expert Rev Clin Immunol. 2015 Aug 2;:1-10

Authors: Mohammadinejad P, Ataeinia B, Kaynejad K, Zeinoddini A, Sadeghi B, Hosseini M, Rezaei N, Aghamohammadi A

Abstract
OBJECTIVES: We aimed to investigate the antimicrobial susceptibility among bacterial isolates of patients with primary immunodeficiency disorders (PID) in comparison with immunocompetent patients.
METHODS: Patients’ antibiotic sensitivity profiles were extracted from their medical records. In order to compare the antibiotic sensitivity profiles of PID patients with immunocompetent patients, the results of antibiograms of patients who did not have a known or suspected immunodeficiency and were hospitalized during the same period were obtained and used as control subjects.
RESULTS: A total number of 257 isolates were obtained from 86 PID patients. Antimicrobial susceptibilities of several organisms isolated from PID patients were significantly lower compared to that of immunocompetent patients.
CONCLUSION: Antibiotic resistance seems to be higher among PID patients compared to immunocompetent patients. This indicates a need for further investigations for the possible factors responsible for antibiotic resistance in PID patients.

PMID: 26234890 [PubMed – as supplied by publisher]

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B Lymphocyte-Specific Loss of Ric-8A Results in a Gα Protein Deficit and Severe Humoral Immunodeficiency.

J Immunol. 2015 Jul 31;

Authors: Boularan C, Hwang IY, Kamenyeva O, Park C, Harrison K, Huang Z, Kehrl JH

Abstract
Resistance to inhibitors of cholinesterase 8A (Ric-8A) is a highly evolutionarily conserved cytosolic protein initially identified in Caenorhabditis elegans, where it was assigned a regulatory role in asymmetric cell divisions. It functions as a guanine nucleotide exchange factor for Gαi, Gαq, and Gα12/13 and as a molecular chaperone required for the initial association of nascent Gα subunits with cellular membranes in embryonic stem cell lines. To test its role in hematopoiesis and B lymphocytes specifically, we generated ric8(fl/fl)vav1-cre and ric8(fl/fl)mb1-cre mice. The major hematopoietic cell lineages developed in the ric8(fl/fl)vav1-cre mice, notwithstanding severe reduction in Gαi2/3, Gαq, and Gα13 proteins. B lymphocyte-specific loss of Ric-8A did not compromise bone marrow B lymphopoiesis, but splenic marginal zone B cell development failed, and B cells underpopulated lymphoid organs. The ric8(fl/fl)mb1-cre B cells exhibited poor responses to chemokines, abnormal trafficking, improper in situ positioning, and loss of polarity components during B cell differentiation. The ric8(fl/fl)mb1-cre mice had a severely disrupted lymphoid architecture and poor primary and secondary Ab responses. In B lymphocytes, Ric-8A is essential for normal Gα protein levels and is required for B cell differentiation, trafficking, and Ab responses.

PMID: 26232433 [PubMed – as supplied by publisher]

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Regulatory B cells in CVID patients fail to suppress multifunctional IFN-γ(+)TNF-α(+)CD4(+) T cells differentiation.

Clin Immunol. 2015 Jul 29;160(2):292-300

Authors: Vlkova M, Ticha O, Nechvatalova J, Kalina T, Litzman J, Mauri C, Blair PA

Abstract
Common variable immunodeficiency (CVID) refers to primary hypogammaglobulinemia with unknown pathogenesis. Although there is evidence for intrinsic B cell defects in some CVID patient groups, various abnormalities in cytokine production by T cells in CVID patients are frequently observed. Here, we demonstrate a relationship in the production of pro-inflammatory Th1 cytokines and regulatory B cells producing IL-10 between CVID patients and healthy controls. We describe CD19(+)CD24(hi)CD38(hi)IL-10(+) regulatory B cells generated after T cell stimulation of human peripheral blood lymphocytes ex vivo are able to suppress IFN-γ(+)TNF-α(+) producing CD4(+) T cells. This process is impaired in CVID patients, who present with both low numbers of CD19(+)CD24(hi)CD38(hi)IL-10(+) B cells and increased numbers of IFN-γ(+)TNF-α(+)CD4(+) T cells. Disruption of the regulatory B cell response to T cell stimulation explains the excessive T cell activation regarded as an immunoregulatory abnormality that is a frequent finding in CVID patients.

PMID: 26232673 [PubMed – as supplied by publisher]

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Streptococcus pneumoniae antibody titres in patients with primary antibody deficiency receiving intravenous immunoglobulin (IVIG) compared to subcutaneous immunoglobulin (SCIG).

Clin Exp Immunol. 2015 Jun 9;

Authors: Knutsen AP, Leiva LE, Caruthers C, Rodrigues J, Sorensen RU

Abstract
Intravenous immunoglobulin (IVIG) and subcutaneous immunoglobulin (SCIG) are effective in the treatment of patients with primary antibody deficiency disorders (PAD). The purpose of this study was to evaluate Streptococcus pneumoniae (Spn) antibody titres to 14 serotypes in patients receiving IVIG compared to SCIG and to correlate Spn antibody levels to clinical outcome. The doses of immunoglobulin (Ig)G/kg/month were similar in both IVIG and SCIG groups. In 11 patients treated with IVIG, Spn antibody titres were ≥ 1·3 μg/ml to 99·4 ± 2·1% of the 14 serotypes at peak IVIG but decreased to 66·9 ± 19·8% at trough IVIG. Loss of Spn titres ≥ 1·3 μg/ml was most frequent for Spn serotypes 1, 4, 9V and 23. This correlated with lower Spn antibody titres to these serotypes at peak IVIG compared to the other serotypes. In 13 patients treated with SCIG, Spn antibody titres were protective to 58·2 ± 23·3% of the serotypes 3-5 days after infusion, similar to trough IVIG. Similarly, the Spn serotypes with the least protective percentages were the same as the ones observed in trough IVIG. There were no annualized serious bacterial infections (aSBI) in either group. However, there were significantly decreased annualized other infections (aOI) in the SCIG group compared to the IVIG-treated group, 0·8 ± 0·7 versus 2·2 ± 1·2 infections/patient/year (P = 0·004). Breakthrough aOI did not correlate with protective or higher serum Spn antibody titres.

PMID: 26230522 [PubMed – as supplied by publisher]

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Related Articles

Atopic dermatitis in children: clinical features, pathophysiology, and treatment.

Immunol Allergy Clin North Am. 2015 Feb;35(1):161-83

Authors: Lyons JJ, Milner JD, Stone KD

Abstract
Atopic dermatitis (AD) is a chronic, relapsing, highly pruritic skin condition resulting from disruption of the epithelial barrier and associated immune dysregulation in the skin of genetically predisposed hosts. AD generally develops in early childhood, has a characteristic age-dependent distribution and is commonly associated with elevated IgE, peripheral eosinophilia, and other allergic diseases. Medications such as antihistamines have demonstrated poor efficacy in controlling AD-associated itch. Education of patients regarding the primary underlying defects and provision of a comprehensive skin care plan is essential for disease maintenance and management of flares.

PMID: 25459583 [PubMed – indexed for MEDLINE]

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