Manish Butte

Clinical, Immunological, and Molecular Findings in Four Cases of B Cell Expansion With NF-κB and T Cell Anergy Disease for the First Time From India.

Front Immunol. 2018;9:1049

Authors: Gupta M, Aluri J, Desai M, Lokeshwar M, Taur P, Lenardo M, Bergerson J, Dalvi A, Mhatre S, Kulkarni M, Kambli P, Madkaikar M

Abstract
B cell expansion with NF-κB and T cell anergy (BENTA) is a rare primary immunodeficiency disorder caused by mutations in the CARD11 gene and results in constitutive NF-κB activation in B and T cells. Affected patients present with polyclonal expansion of B cells at an early age with splenomegaly, lymphadenopathy, and mild autoimmunity. Here, we discuss four BENTA cases with unusual clinical manifestations not previously reported. All patients showed previously reported gain-of-function mutations (G123S, G123D, and C49Y) in the CARD11 gene. Severe autoimmune manifestations were noted for the first time in all our patients.

PMID: 29963038 [PubMed]

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Recommendations for the management of tuberculosis in children – KOMPASS TB. Part 1: Tuberculosis prevention.

Adv Respir Med. 2018;86(3):

Authors: Bielecka T, Augustynowicz-Kopeć E, Gonerko P, Gruszczyński P, Korzeniewska-Koseła M, Krasińska M, Krenke K, Lange J, Pankowska A, Popielarz M, Pustkowski A, Stryczyńska-Kazubska J, Doniec Z

Abstract
Since the second half of the 20th century the incidence of tuberculosis has been declining in Poland. Despite this, current epidemiological data still support the need for the continued mass BCG vaccination in Poland in the near future. Apart from the protection against severe hematogenous forms of tuberculosis, vaccination lowers the risk of infection with Mycobacterium tuberculosis. Primary and acquired immunodeficiency, including immunity disorders associated with an ongoing treatment, are contraindications to BCG vaccination. The most common adverse effects following BCG vaccination are reactions at the site of injection and in regional lymph nodes, which usually does not require treatment. Methods of tuberculosis prevention, particularly recommended in low-incidence countries, include: diagnostic investigations of patients who had contacts with pulmonary tuberculosis as well as an active detection and treatment of latent Mycobacterium tuberculosis infection. Latent tuberculosis infection can be identified on the basis of positive results of the tuberculin skin test or interferon-gamma release assays after the active disease has been ruled out. This condition does require prophylactic treatment.

PMID: 29960282 [PubMed – in process]

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Biweekly Hizentra® in Primary Immunodeficiency: a Multicenter, Observational Cohort Study (IBIS).

J Clin Immunol. 2018 Jun 28;:

Authors: Vultaggio A, Azzari C, Ricci S, Martire B, Palladino V, Gallo V, Pecoraro A, Pignata C, Spadaro G, Graziani S, Moschese V, Trizzino A, Boggia GM, Matucci A

Abstract
Immunoglobulin G (IgG) replacement therapy is a standard treatment for patients with primary immunodeficiency diseases (PIDs). Hizentra®, a 20% human subcutaneous IgG (SCIG), is approved for biweekly administration for PIDs. The aim of the multicenter IBIS study was to prospectively investigate the efficacy of biweekly Hizentra® compared with previous IVIG or SCIG treatment regimens in patients with PIDs. The study consisted of a 12-month retrospective period followed by 12-month prospective observational period. The main endpoints included pre-infusion IgG concentrations, proportion of patients with serious bacterial infections (SBIs), other infections, hospitalizations due to PID-related illnesses, and days with antibiotics during the study periods. Of the 36 patients enrolled in the study, 35 patients continued the study (mean age 26.1 ± 14.4 years; 68.6% male). The mean pre-infusion IgG levels for prior immunoglobulin regimens during the retrospective period (7.84 ± 2.09 g/L) and the prospective period (8.55 ± 1.76 g/L) did not show any significant variations (p = 0.4964). The mean annual rate of SBIs/patient was 0.063 ± 0.246 for both prospective and retrospective periods. No hospitalizations related to PIDs were reported during the prospective period versus one in the retrospective period. All patients were either very (76.5%) or quite (23.5%) satisfied with biweekly Hizentra® at the end of the study. In conclusion, the IBIS study provided real-world evidence on the efficacy of biweekly Hizentra® in patients with PIDs, thus verifying the data generated by the pharmacometric modeling and simulation study in a normal clinical setting.

PMID: 29951948 [PubMed – as supplied by publisher]

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Cost-effectiveness analysis of subcutaneous immunoglobulin replacement therapy in Iranian patients with primary immunodeficiencies.

Med J Islam Repub Iran. 2017;31:94

Authors: Shabaninejad H, Asgharzadeh A, Rezapour A, Rezaei N

Abstract
Background: Economic evaluation of subcutaneous immunoglobulin therapy (SCIG) is important, and it has recently been used for treatment of patients with primary immunodeficiency (PID) diseases, and can improve allocation of resources in health care systems. The present research aimed at providing an economic assessment of SCIG and IVIG (intravenous immunoglobulin therapy) administration in Iran. Methods: Data related to clinical effectiveness were obtained from a meta-analysis. Economic analysis was performed taking into account the perspective of health care providers. Incremental cost-effectiveness ratio (ICER) was applied for economic evaluation of the 2 methods, and GDP per capita was considered as a threshold. Results: The results of meta-analysis suggested a higher effectiveness of SCIG compared to IVIG in serum immunoglobulin (Ig) levels (SMD= 0.336) and adverse effects (OR= 0.497), while the cost of IVIG was higher than SCIG ($1370 vs. $121). The ICER obtained in this paper ($2939 for adverse effects and $4348 for serum Ig level) was less than the GDP per capita in Iran ($4,916.10), and thus SCIG is a more cost-effective therapy for PID patients. Conclusion: Switching from IVIG to SCIG is cost-effective for PID patients and is approved by the health care providers’ points of view in this study.

PMID: 29951395 [PubMed]

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Adverse Effects of Immunoglobulin Therapy.

Front Immunol. 2018;9:1299

Authors: Guo Y, Tian X, Wang X, Xiao Z

Abstract
Immunoglobulin has been widely used in a variety of diseases, including primary and secondary immunodeficiency diseases, neuromuscular diseases, and Kawasaki disease. Although a large number of clinical trials have demonstrated that immunoglobulin is effective and well tolerated, various adverse effects have been reported. The majority of these events, such as flushing, headache, malaise, fever, chills, fatigue and lethargy, are transient and mild. However, some rare side effects, including renal impairment, thrombosis, arrhythmia, aseptic meningitis, hemolytic anemia, and transfusion-related acute lung injury (TRALI), are serious. These adverse effects are associated with specific immunoglobulin preparations and individual differences. Performing an early assessment of risk factors, infusing at a slow rate, premedicating, and switching from intravenous immunoglobulin (IVIG) to subcutaneous immunoglobulin (SCIG) can minimize these adverse effects. Adverse effects are rarely disabling or fatal, treatment mainly involves supportive measures, and the majority of affected patients have a good prognosis.

PMID: 29951056 [PubMed]

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Clearing Vaccine-Derived Poliovirus Infection Following Hematopoietic Stem Cell Transplantation: a Case Report and Review of Literature.

J Clin Immunol. 2018 Jun 14;:

Authors: Shaghaghi M, Irannejad M, Abolhassani H, Shahmahmoodi S, Hamidieh AA, Soleyman-Jahi S, Yazdani R, Azizi G, Aghamohammadi A

Abstract
The use of oral poliovirus vaccine in a worldwide scale has led to a 99.9% decrease in annual incidence of wild-type poliomyelitis and the eradication of serotype 2 poliovirus. However, the emergence of vaccine-derived polioviruses (VDPVs) is endangering the eradication program. Patients with combined immunodeficiencies are at increased risk of both vaccine-associated poliomyelitis and prolonged asymptomatic infection with immunodeficiency-associated VDPVs (iVDPVs). Herein, we present a severe combined immunodeficiency patient with prolonged and asymptomatic iVDPV infection. He continued to shed poliovirus during immunoglobulin replacement therapy and cleared the infection following successful hematopoietic stem cell transplantation (HSCT). To explain the efficiency of HSCT in clearing the infection, we reviewed the literature for all reports of HSCT in iVDPV-excreting patients and discussed novel ideas about the role of different immune mechanisms, including cell-mediated interactions, in mounting immune responses against poliovirus infections. This study could provide further insights into the immune mechanisms contributing to the clearance of enteroviral infections.

PMID: 29948575 [PubMed – as supplied by publisher]

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Correlation between flow cytometry and molecular findings in autosomal recessive chronic granulomatous disease: A cohort study from Oman.

Int J Lab Hematol. 2018 Jun 26;:

Authors: Al-Riyami AZ, Al-Zadjali S, Al-Mamari S, Al-Said B, Al-Qassabi J, Al-Tamemi S

Abstract
BACKGROUND: Chronic granulomatous disease (CGD) is an X-linked (XL) or autosomal recessive (AR) primary immunodeficiency disease. Respiratory burst assessment by flow cytometry is a rapid test of granulocyte stimulation, and results predict the underlying genotype. This study aims to describe the immune-phenotypic profile of patients with CGD diagnosed in our center and correlate that with underlying genetic mutations.
METHODS: Immuno-phenotypic and genetic data on all patients with CGD diagnosed at Sultan Qaboos University Hospital (SQUH) were reviewed.
RESULTS: A total of 32 patients were diagnosed with CGD using molecular studies. Genetically confirmed individuals included 1 patient with XL-CGD (a large deletion involving the CYBB and XK genes resulting in a McLeod phenotype), 27 patients with AR-CGD with a c.579G>A (p.Trp193X) mutation at the NCF1 gene, and 4 patients with AR-CGD with a c.784G>A (p.Gly262Ser) mutation at the NCF1 gene. Flow cytometry and molecular results were available for comparison in 26 patients with AR-CGD. The patients with AR-CGD had a range of flow cytometry-generated fluorescent patterns as follows: reduced neutrophil stimulation with a sharp peak (12/26), reduced neutrophil stimulation with a broad peak (11/26), and a complete lack of neutrophil stimulation (3/26). No consistent flow cytometry-generated fluorescent pattern was observed in either of the 2 AR mutations identified in our patients.
CONCLUSION: Flow cytometry is a robust test of CGD diagnosis. However, results should be interpreted with caution when predicting the underlying probable genotype, and results need to be complemented with definitive molecular studies.

PMID: 29947158 [PubMed – as supplied by publisher]

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Prevalence of Cryptosporidium, Blastocystis, and other opportunistic infections in patients with primary and acquired immunodeficiency.

Parasitol Res. 2018 Jun 26;:

Authors: Bednarska M, Jankowska I, Pawelas A, Piwczyńska K, Bajer A, Wolska-Kuśnierz B, Wielopolska M, Welc-Falęciak R

Abstract
Intestinal opportunistic infections are often caused by unicellular parasites. Individuals with decreased immunity are particularly susceptible to infection by said microorganisms, and when they are infected, diarrhea can be the main clinical manifestation. However, intestinal parasites have rarely been taken into account in intestinal disorders. In our study, an investigation was conducted to determine the prevalence of intestinal micro-pathogens, such as Cryptosporidium, Giardia, Blastocystis, and microsporidia, in hospitalized patients with different immunological statuses. The study at hand indicates that protozoan parasitic infections are rare among immunodeficient patients in Poland. The overall prevalence of micro-pathogens among participants was 4.6%; it was three times higher in adults (12.5%) than in children (2.3%). Cryptosporidium and Cyclospora species (Apicomplexa) were diagnosed as the main cause of heavy diarrhea. Accordingly, adult patients were positive mainly for Blastocystis and microsporidia, while children were more often infected with the Cryptosporidium species.

PMID: 29946765 [PubMed – as supplied by publisher]

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