Single-Center Study of 72 Patients with Severe Combined Immunodeficiency: Clinical and Laboratory Features and Outcomes.

Severe combined immunodeficiency is an inborn error of immunity characterized by impairments in the numbers and functions of T and B lymphocytes due to various genetic causes, and if it remains untreated, patients succumb to infections during the first 2 years of life. PURPOSE AND METHODS: This study reported retrospective data from 72 infants diagnosed with SCID including their major clinical features, HSCT characteristics, and outcomes over a 20-year period (1997-2017). RESULTS: Sixty-one of 72 SCID patients in the study underwent HSCT from 1997 to 2017. Median ages at the time of diagnosis and transplantation were 3.5 months and 5 months, respectively. Consanguinity was present in 68% of the patients, and T - B - NK + phenotype was predominantly identified. The overall survival was 80.3% over a 20-year period. However, the patients transplanted during an active infection had a lower survival rate of 73.9% compared to 100% for patients transplanted infection-free or with a previous infection that had resolved. The survival rate was significantly higher among recipients of HLA-identical transplants (92.9%), compared to recipients of mismatched related transplants (70%). The overall survival increased from 50 (1997-2006) to 85% (2007-2017) during the last 10 years. CONCLUSIONS: This is one of the largest single-center studies in Turkey with extensive experience about SCID patients. Early diagnosis of SCID patients before the onset of an infection and early transplantation are shown to be extremely important factors affecting the outcome and increasing the survival regardless of the donor type based on the results of this study.

Growth, tolerance and safety outcomes with use of an extensively hydrolyzed casein-based formula in infants with cow's milk protein allergy.

Objective: To evaluate growth, tolerance and safety outcomes with use of an extensively hydrolyzed casein-based formula (eHCF) in infants with cow's milk protein allergy (CMPA). Methods: A total of 226 infants (mean ± SD age: 106.5 ± 39.5 days, 52.7% were girls) with CMPA who received eHCF comprising at least half of the daily dietary intake were included. Data on anthropometrics [weight for age (WFA), length for age (LFA) and weight for length (WFL) z-scores] were recorded at baseline (visit 1), while data on infant feeding and stool records, anthropometrics and Infant Feeding and Stool Patterns and Formula Satisfaction Questionnaires were recorded at visit 2 (on Days 15 ± 5) and visit 3 (on Days 30 ± 5). Results: From baseline to visit 2 and visit 3, WFA z-scores (from -0.60 ± 1.13 to -0.54 ± 1.09 at visit 2, and to -0.44 ± 1.05 at visit 3, p < 0.001) and WFL z-scores (from -0.80 ± 1.30 to -0.71 ± 1.22 at visit 2, and to -0.64 ± 1.13 at visit 3, p = 0.002) were significantly increased. At least half of infants never experienced irritability or feeding refusal (55.7%) and spit-up after feeding (50.2%). The majority of mothers were satisfied with the study formula (93.2%), and wished to continue using it (92.2%). Conclusions: In conclusion, eHCF was well-accepted and tolerated by an intended use population of infants ≤ 6 months of age with CMPA and enabled adequate volume consumption and improved growth indices within 30 days of utilization alongside a favorable gastrointestinal tolerance and a high level of parental satisfaction.

HLA-haploidentical transplantations for primary immunodeficiencies: a single-center experience.

SCID is characterized by profound deficiencies of T and B lymphocytes. HSCT is the only curative treatment for children with SCID. The clinical characteristics and outcome of 30 HLA-haploidentical transplantations in 18 patients (15 SCID, two Omenn syndrome, and one MHC Class II deficiency) are reported here. The age of patients at diagnosis ranged from one and half to nine months (median: four months). The median time was one month between the diagnosis and the time of the initial transplantation. Infused CD34+ stem cell dose was ranged between 7 and 94.2 × 10(6) /kg. Nine of 18 patients were found to be positive for CMV antigenemia at diagnosis; therefore, none of them received a conditioning regimen. The most common complication was graft failure (61%), so repeated transplantations (two to four) were performed in seven patients. The mean time of lymphoid engraftment was 17.5 days (median: 16, range: 11-29 days). Ten of 15 SCID (67%) patients survived with a stable complete donor chimerism. However, all three non-SCID patients died. In conclusion, in the absence of a matched family donor, HLA-haploidentical transplantation from parental donors represents a readily available treatment option especially for patients with SCID, offering a high chance of cure.

Regulatory T cell levels in children with asthma.

Natural regulatory T (nTreg) cells are described by expression of a specific transcription factor, FOXP3, on CD4+CD25+ cells. They play very important roles in the suppression of allergic reactions and disorders. The aim of this study was to obtain peripheral blood Treg levels among atopic asthmatic patients before and during inhaled steroid treatment and to observe the effect of these cells on the pathogenesis and treatment of asthma. CD4+CD25+FOXP3+ T cells obtained from 20 healthy donors and from 16 atopic asthmatic patients before and after inhaled glucocorticoid treatment were examined by flow cytometer. The levels of CD4+CD25+ FOXP3+ Treg cells were higher in asthmatic children who had been receiving inhaled glucocorticoids, when compared to the control group and to the patients' levels before treatment (p<0.05). The present study suggests that at least one of the anti-inflammatory effects of inhaled glucocorticoids in asthma depends upon induction of Treg cells.

Defects along the T(H)17 differentiation pathway underlie genetically distinct forms of the hyper IgE syndrome.

BACKGROUND: The hyper IgE syndrome (HIES) is characterized by abscesses, eczema, recurrent infections, skeletal and connective tissue abnormalities, elevated serum IgE, and diminished inflammatory responses. It exists as autosomal-dominant and autosomal-recessive forms that manifest common and distinguishing clinical features. A majority of those with autosomal-dominant HIES have heterozygous mutations in signal transducer and activator of transcription (STAT)-3 and impaired T(H)17 differentiation. OBJECTIVE: To elucidate mechanisms underlying different forms of HIES. METHODS: A cohort of 25 Turkish children diagnosed with HIES were examined for STAT3 mutations by DNA sequencing. Activation of STAT3 by IL-6 and IL-21 and STAT1 by IFN-alpha was assessed by intracellular staining with anti-phospho (p)STAT3 and -pSTAT1 antibodies. T(H)17 and T(H)1 cell differentiation was assessed by measuring the production of IL-17 and IFN-gamma, respectively. RESULTS: Six subjects had STAT3 mutations affecting the DNA binding, Src homology 2, and transactivation domains, including 3 novel ones. Mutation-positive but not mutation-negative subjects with HIES exhibited reduced phosphorylation of STAT3 in response to cytokine stimulation, whereas pSTAT1 activation was unaffected. Both patient groups exhibited impaired T(H)17 responses, but whereas STAT3 mutations abrogated early steps in T(H)17 differentiation, the defects in patients with HIES with normal STAT3 affected more distal steps. CONCLUSION: In this cohort of Turkish children with HIES, a majority had normal STAT3, implicating other targets in disease pathogenesis. Impaired T(H)17 responses were evident irrespective of the STAT3 mutation status, indicating that different genetic forms of HIES share a common functional outcome.

Primary immune deficiency disease awareness among a group of Turkish physicians.

Primary immunodeficiencies (PIDs) are a relatively common occurrence in countries where consanguineous marriages are widespread. A principal factor leading to misdiagnosis and ensuing complications can be the lack of knowledge and proper evaluation. The aim of this study was to assess PID awareness and the identification of diagnostic criteria leading to correct diagnosis. Seven hundred eighty-six questionnaires with 71 items were distributed to physicians attending the 41st National Congress of Pediatrics (2005) and to pediatric residents of two university hospitals from different cities in Turkey. The 217 completed questionnaires revealed that family history (91.2%), consanguineous marriages (87.1%), infant deaths (70.0%), persistent thrush (90.3%), hospitalization for recurrent cellulitis (70.5%), chronic diarrhea due to giardiasis (62.2%), recurrent oral aphthous lesions (58.5%), telangiectasia (82.0%), failure to thrive (78.8%), absence of tonsil tissue (74.7%), oculocutaneous albinism (73.7%), and resistant sinusitis (71.0%) were cited among important indicators of PID. However, neonatal tetany (77.9%), liver abscess (61.3%) and poliomyelitis following oral polio vaccination (51.2%) were not considered as related to PID. Although white blood cell (WBC) and differential were chosen as the preferred initial tests, leukocytosis and lymphopenia were also not judged as related to PID. More comprehensive pre/postgraduate education in PID appears to be necessary for physicians in Turkey.

[TGF-Beta1-915G/C and TNF-alpha-308G/A polymorphisms in children with asthma]. / Astimli çocuklarda TGF-Beta1-915G/C ve TNF-alpha-308G/A polimorfizmleri.

TGF-Beta1 is a pro and antiinflammatory cytokine and plays an important role in airway remodelling in asthma. TNF-alpha is a proinflammatory cytokine that involved in the pathogenesis of asthma. Cytokine production is under genetic control, and certain single nucleotide polymorphisms (SNPs), which lead to allelic variants of cytokine genes are associated with higher or lower cytokine production in vitro. In some studies TGF-Beta1-915G/C and TNF-alpha-308G/A polymorphisms are found to be more prevalent and associated with asthma. The aim of this study is to investigate the frequency of TGF-Beta1-915G/C and TNF-alpha-308G/A polymorphisms and to determine whether or not these polymorphisms are associated with the development of asthma in children. 46 asthmatic children and 67 healthy controls were investigated by LightCycler PCR analysis for TGF-Beta1-915G/C and TNF-alpha-308G/A polymorphisms. The frequency of TGF-Beta1-915G/C and TNF-alpha-308G/A polymorphisms in asthmatic children were 15.2% and 23.9% respectively while the corresponding figures were 8.9% and 23.8% in the control group (p> 0.05). The risk of asthma development was not associated for TGF-Beta1 915G/C (OR: 0.54, 95% CI: 0.17-1.75) and TNF-alpha-308G/A (OR: 0.99, 95% CI: 0.41-2.40) polymorphisms. These results indicated that, the frequency of TGF-Beta1 915G/C and TNF-alpha-308G/A polymorphisms did not show any difference in asthmatic children compared to healthy controls and these polymorphisms do not seem to influence suspectibilty to asthma.

An unconditioned bone marrow transplantation in a child with purine nucleoside phosphorylase deficiency and its unique complication.

Purine nucleoside phosphorylase deficiency is a rare immunodeficiency syndrome characterized by recurrent infections, neurological dysfunction, and autoimmunity. Early diagnosis and hematopoietic stem cell transplantation may reverse the dismal prognosis in PNP deficiency. This report presents a new PNP deficiency case successfully transplanted without a conditioning regimen from an HLA-identical family donor, who developed a complication of disseminated BCG infection.