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20% subcutaneous immunoglobulin for patients with primary immunodeficiency diseases: A systematic review.

January 31, 2015 By Manish Butte

20% subcutaneous immunoglobulin for patients with primary immunodeficiency diseases: A systematic review.

Int Immunopharmacol. 2015 Jan 26;

Authors: Song J, Zhang L, Li Y, Quan S, Liang Y, Zeng L, Liu Y

Abstract
BACKGROUND: Primary immunodeficiency diseases (PID) are a group of rare disorders that patients do not have normal function of the immune system. Subcutaneous immunoglobulin 20% (SCIG-20%) was a candidate when considering replacement therapy with immunoglobulin in PID, but the evidence was not clear. To understand and interpret the available evidence, we conducted a systematic review to assess the efficacy and safety of SCIG-20% for patients with PID.
METHOD: Literature searches were conducted in PUBMED, EMBASE, Cochrane Library, CBM, VIP, CNKI, WanFang, LILACS and U.S. ClinicalTrials.gov. Clinical studies published in full text that met predefined inclusion criteria were eligible irrespective of language. Reviewers independently assessed all potential studies and extracted data. The fixed-effect model was used in meta-analysis.
RESULTS: 4 studies involving 100 patients were included. The pooled rate of infection was 0.80 with the annual rate of 3.74. 38% patients missed days from work/school and annual rate was 4.54days in one year per patient. Only 4% patients were hospitalized due to infection and it costs 1.57days in one year per patient. 70% patients used antibiotics during 58.4days in one year per patient. 80 patients (80.0%) who experienced 1630 AEs were considered related to SCIG-20%. Only 7 related AEs were severe, of which, 4 were local reactions and 3 were headaches. Studies on health related quality of life and satisfaction suggested that patients with SCIG-20% had a good life quality and satisfied with SCIG treatment.
CONCLUSIONS: SCIG-20% treatment was not recommended for patients with primary immunodeficiency. Low quality of each outcome suggested that the evidence on effect of SCIG-20% for patients with PID is inadequate. Further comparative studies are urgently needed, especially in comparison with IVIG or SCIG of other concentrations.

PMID: 25633961 [PubMed – as supplied by publisher]

Antibody Levels to Bordetella pertussis and Neisseria meningitidis in Immunodeficient Patients Receiving Immunoglobulin Replacement Therapy.

January 30, 2015 By Manish Butte

Antibody Levels to Bordetella pertussis and Neisseria meningitidis in Immunodeficient Patients Receiving Immunoglobulin Replacement Therapy.

J Clin Immunol. 2015 Jan 29;

Authors: Adam E, Church JA

Abstract
PURPOSE: Patients with antibody deficiency rely on immunoglobulin products for protection against many vaccine-preventable diseases. We measured antibody titers against Bordetella pertussis and Neisseria meningitidis in patients receiving immunoglobulin (IG) therapy to determine if they have any protection against infections from these organisms.
METHODS: In an unblinded, prospective assessment we measured antibody titers against B. pertussis filamentous hemagglutinin (FHA) and pertussis toxin (PT) antigens and N. meningitidis serogroups A, C, W-135, and Y in patients receiving immunoglobulin therapy for primary immune deficiency (PI). We measured steady state levels in patients receiving subcutaneous immunoglobulin therapy while in patients receiving intravenous immunoglobulin therapy we measured titers immediately before and after infusion to more clearly define the contribution of the infused product.
RESULTS: Thirty subjects, 17 females and 13 males, participated in the study, 22 were receiving intravenous IG products and 8 were receiving subcutaneous IG products. Diagnoses included common variable immunodeficiency in 12, combined immunodeficiency in 6, specific antibody deficiency in 6, X-linked agammaglobulinemia in 4 and ataxia telangiectasia and hyper-IgE syndrome in one each. All subjects had detectable IgG antibodies against the pertussis antigens measured and most had antibody to the meningococcus serotypes measured. However, only 26.6 % had protective levels (>= 2 mcg/mL) against serogroup C at trough or steady state.
CONCLUSIONS: Patients receiving immunoglobulin therapy have antibodies against B. pertussis and most of them have antibodies against the four measured serogroups of N. meningitidis. There is significant variability in the levels of antibody between patients and the low titers against group C may suggest a role for active immunization in those who may respond to conjugated polysaccharide vaccine administration.

PMID: 25631528 [PubMed – as supplied by publisher]

Mechanisms of action of Ig preparations: immunomodulatory and anti-inflammatory effects.

January 30, 2015 By Manish Butte

Mechanisms of action of Ig preparations: immunomodulatory and anti-inflammatory effects.

Front Immunol. 2014;5:690

Authors: Matucci A, Maggi E, Vultaggio A

Abstract
Primary immunodeficiency (PID) disorders that predispose patients to recurrent infections require immunoglobulin (Ig) replacement therapy. Ig replacement therapy has been stated as beneficial, although the optimal IgG trough level to be maintained over time in order to minimize infectious risk has not been established. The most common route of administration of Ig has been intravenously, although there are different options, one of them being the subcutaneous route. Ig replacement therapy has been a life-saving treatment for patients suffering from primary and secondary antibody immunodeficiency. The key role of regular Ig replacement in patients with antibody deficiencies is related to the ability to provide specific antibodies that could not be produced by these patients as demonstrated by the reduction of severe infections such as meningitis and pneumonia. The therapeutic benefits of Ig may also be due to an active role in various anti-inflammatory and immunomodulatory activities, which may complicate the clinical picture of PID. Anti-inflammatory activities are seen more generally when intravenous Ig is administered at high dose. The immunomodulatory and anti-inflammatory activities are important not only in the treatment of autoimmune diseases but also in patients suffering from immunodeficiency.

PMID: 25628625 [PubMed]

BAY 41-2272 activates host defence against local and disseminated Candida albicans infections.

January 30, 2015 By Manish Butte

BAY 41-2272 activates host defence against local and disseminated Candida albicans infections.

Mem Inst Oswaldo Cruz. 2015 Jan 23;:0

Authors: Soeiro-Pereira PV, Falcai A, Kubo CA, Antunes E, Condino-Neto A

Abstract
In our previous study, we have found that 5-cyclopropyl-2-[1-(2-fluoro-benzyl)-1H-pyrazolo[3,4-b]pyridine-3-yl]-pyrimidin-4-ylamine (BAY 41-2272), a guanylate cyclase agonist, activates human monocytes and the THP-1 cell line to produce the superoxide anion, increasing in vitro microbicidal activity, suggesting that this drug can be used to modulate immune functioning in primary immunodeficiency patients. In the present work, we investigated the potential of the in vivo administration of BAY 41-2272 for the treatment of Candida albicans and Staphylococcus aureus infections introduced via intraperitoneal and subcutaneous inoculation. We found that intraperitoneal treatment with BAY 41-2272 markedly increased macrophage-dependent cell influx to the peritoneum in addition to macrophage functions, such as spreading, zymosan particle phagocytosis and nitric oxide and phorbol myristate acetate-stimulated hydrogen peroxide production. Treatment with BAY 41-2272 was highly effective in reducing the death rate due to intraperitoneal inoculation of C. albicans, but not S. aureus. However, we found that in vitro stimulation of peritoneal macrophages with BAY 41-2272 markedly increased microbicidal activities against both pathogens. Our results show that the prevention of death by the treatment of C. albicans-infected mice with BAY 41-2272 might occur primarily by the modulation of the host immune response through macrophage activation.

PMID: 25626456 [PubMed – as supplied by publisher]

Acute neonatal infections 'lock-in' a suboptimal CD8+ T cell repertoire with impaired recall responses.

January 28, 2015 By Manish Butte

Acute neonatal infections ‘lock-in’ a suboptimal CD8+ T cell repertoire with impaired recall responses.

PLoS Pathog. 2013 Sep;9(9):e1003572

Authors: Rudd BD, Venturi V, Smith NL, Nzingha K, Goldberg EL, Li G, Nikolich-Zugich J, Davenport MP

Abstract
Microbial infection during various stages of human development produces widely different clinical outcomes, yet the links between age-related changes in the immune compartment and functional immunity remain unclear. The ability of the immune system to respond to specific antigens and mediate protection in early life is closely correlated with the level of diversification of lymphocyte antigen receptors. We have previously shown that the neonatal primary CD8+ T cell response to replication competent virus is significantly constricted compared to the adult response. In the present study, we have analyzed the subsequent formation of neonatal memory CD8+ T cells and their response to secondary infectious challenge. In particular, we asked whether the less diverse CD8+ T cell clonotypes that are elicited by neonatal vaccination with replication competent virus are ‘locked-in’ to the adult memory T cell, and thus may compromise the strength of adult immunity. Here we report that neonatal memory CD8+ T cells mediate poor recall responses compared to adults and are comprised of a repertoire of lower avidity T cells. During a later infectious challenge the neonatal memory CD8+ T cells compete poorly with the fully diverse repertoire of naïve adult CD8+ T cells and are outgrown by the adult primary response. This has important implications for the timing of vaccination in early life.

PMID: 24068921 [PubMed – indexed for MEDLINE]

[A case of autoimmune lymphoproliferactive syndrome and literature review.]

January 27, 2015 By Manish Butte

[A case of autoimmune lymphoproliferactive syndrome and literature review.]

Zhonghua Er Ke Za Zhi. 2014 Dec;52(12):923-926

Authors: Liu L, Hu J, Ma J, Li X, Li F, Li C

Abstract
OBJECTIVE: To summarize the clinical characteristics, diagnosis and treatment of a case with autoimmune lymphoproliferative syndrome (ALPS) .
METHOD: The patient was diagnosed as autoimmune lymphoproliferactive syndrome (ALPS) after being admitted to the Department of Rheumatism and Immunology of Tianjin Children’s Hospital in February 20, 2014. The clinical characteristics, physical examination, laboratory tests, gene tests, and treatment process were analyzed and related literature was reviewed.
RESULT: The patient was a 16-month- old boy.Since the first month of life, he started to have repeatedly fever, diarrhea, shortness of breath, lymphadenopathy, hepatosplenomegaly, anemia (HGBmin 50 g/L) and thrombocytopenia (min 35×10(9)/L) . But multiple exams showed a normal peripheral blood leukocyte count, hypergammaglobulinemia (IgG 19 800 mg/L, IgA 1 710 mg/L, IgM 2 590 mg/L) and significantly increased serum vitamin B12. Flow cytometric measures showed that CD3(+) CD4(-)CD8(-) T lymphocytes significantly increased ( > 10%) at four times. The count of CD3(+)TCRαβ(+)CD4(-)CD8(-)T lymphocytes (double negative T cells; DNTs) >3% twice. The genetic test showed that 309th FAS gene area showed heterozygous mutations, the boy was diagnosed as ALPS. Added examinations of lymphocytes apoptosis induced by FAS was positive. He was treated with prednisone 15 mg once daily and immunomodulator 150 mg three times a day, while in maintaining period with normal levels of hemoglobin and platelet, the dose of prednisone was reduced gradually. Till now, the patient has been treated and observed for 8 months. We retrieved the reports of ALPS in the databases at home and abroad published in recent 10 years, more than 400 cases reported from foreign countries, but there were only 5 domestic cases. Among those, 4 had onset in infancy and 1 at 6-years of age. All the cases presented servere lymphadenopathy and hepatosplenomegaly with anemia (4 of them with hemolytic anemia) and thrombocytopenia. Three cases had a history of frequent infection, one of them had glomerulonephritis. All patient with significant high level of serum immunoglobulin ( > 1.5 times upper limit of normal range), in 3 of them serum vitamin B12 was > 1.5 pg/L (the other 2 cases missed the exam). In 5 cases CD3(+)CD4(-)CD8(-)T cells > 10%, and in 2 case DNTs were 8.9% and 15.7% respectively (the other 3 cases missed the exam). Three cases were clearly detected with FAS mutations. All patients were treated with corticosteroid, 2 of them were added with mycophenolate mofetil. The therapy presented effective result in early 1-3 months, but no long-term follow-up reports were available.
CONCLUSION: ALPS is a disorder of disrupted lymphocyte homeostasis caused by defective Fas-mediated apoptosis, and it is one of the primary immunodeficiency diseases. The onset of the disease occurs during infancy mainly. Clinical lymphoid hyperplasia and autoimmune phenomena are outstanding signs, which can be associated with frequent infections and allergies. The level of serum vitamin B12 > 1.5 pg/L and the count of CD3(+) CD4(-)CD8(-)T cell show important significance. Exact diagnosis should depend on detecting DNTs and FAS gene.

PMID: 25619350 [PubMed – as supplied by publisher]

[Primary immunodeficiency diseases: challenges and opportunities for Chinese pediatrician.]

January 27, 2015 By Manish Butte

[Primary immunodeficiency diseases: challenges and opportunities for Chinese pediatrician.]

Zhonghua Er Ke Za Zhi. 2014 Dec;52(12):881-884

Authors: Zhao X

PMID: 25619341 [PubMed – as supplied by publisher]

Hemophagocytic lymphohistiocytosis and primary immune deficiency disorders.

January 27, 2015 By Manish Butte

Hemophagocytic lymphohistiocytosis and primary immune deficiency disorders.

Clin Immunol. 2014 Nov;155(1):118-25

Authors: Faitelson Y, Grunebaum E

Abstract
Hemophagocytic lymphohistiocytosis (HLH) is characterized by uncontrolled immune activation and is traditionally associated with inherited gene defects or acquired causes. In addition to abnormalities in cytotoxic granules and lysosomes, various primary immune deficiency disorders (PID) have been identified among patients suffering from HLH. Our purpose was twofold: to better characterize and detail the association between PID and HLH. We found that HLH occurs infrequently among patients with PID, particularly those suffering from abnormalities that impair T cell function. The prognosis of patients suffering from PID and HLH is poor, emphasizing the need for rapid clinical and genetic diagnosis of the PID as well as initiation of appropriate management of the HLH, including allogeneic hematopoietic stem cell transplantations. The association of HLH and PID implicates abnormal T cell function as an important factor in HLH development. It also suggests that the partition of HLH into genetic versus acquired forms might be misleading.

PMID: 25241079 [PubMed – indexed for MEDLINE]

Pulmonary manifestations in adult patients with chronic granulomatous disease.

January 24, 2015 By Manish Butte

Pulmonary manifestations in adult patients with chronic granulomatous disease.

Eur Respir J. 2015 Jan 22;

Authors: Salvator H, Mahlaoui N, Catherinot E, Rivaud E, Pilmis B, Borie R, Crestani B, Tcherakian C, Suarez F, Dunogue B, Gougerot-Pocidalo MA, Hurtado-Nedelec M, Dreyfus JF, Durieu I, Fouyssac F, Hermine O, Lortholary O, Fischer A, Couderc LJ

Abstract
Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by failure of superoxide production in phagocytic cells. The disease is characterised by recurrent infections and inflammatory events, frequently affecting the lungs. Improvement of life expectancy now allows most patients to reach adulthood. We aimed to describe the pattern of pulmonary manifestations occurring during adulthood in CGD patients. This was a retrospective study of the French national cohort of adult patients (⩾16 years old) with CGD. Medical data were obtained for 67 adult patients. Pulmonary manifestations affected two-thirds of adult patients. Their incidence was significantly higher than in childhood (mean annual rate 0.22 versus 0.07, p=0.01). Infectious risk persisted despite anti-infectious prophylaxis. Invasive fungal infections were frequent (0.11 per year per patient) and asymptomatic in 37% of the cases. They often required lung biopsy for diagnosis (10 out of 30). Noninfectious respiratory events concerned 28% of adult patients, frequently associated with a concomitant fungal infection (40%). They were more frequent in patients with the X-linked form of CGD. Immune-modulator therapies were required in most cases (70%). Respiratory manifestations are major complications of CGD in adulthood. Noninfectious pulmonary manifestations are as deleterious as infectious pneumonia. A specific respiratory monitoring is necessary.

PMID: 25614174 [PubMed – as supplied by publisher]

[Common variable immunodeficiency can present as a multisystemic disorder.]

January 24, 2015 By Manish Butte

[Common variable immunodeficiency can present as a multisystemic disorder.]

Ugeskr Laeger. 2015 Jan 26;177(2A)

Authors: Jørgensen RM, Hansen AB, Cannon SV, Peterslund NA

Abstract
Common variable immunodeficiency is the second most common primary immunodeficiency with a prevalence of approx. 1/10.000-50.000. The clinical challenge is early diagnosis and efficient supportive treatment. The purpose of the present article is to focus on the complexity of the disease, including the risk of a long pre-diagnostic period and to focus on the sarcoidosis-like variant and the possible impact of immunoglobulin subclass deficiency.

PMID: 25612949 [PubMed – as supplied by publisher]