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Hans D. Ochs - One of the best experts on this subject based on the ideXlab platform.
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gastrointestinal manifestations in X Linked Agammaglobulinemia
Journal of Clinical Immunology, 2017Co-Authors: Sara Barmettler, Iris M Otani, Jasmit S Minhas, Roshini S Abraham, Yenhui Chang, Morna J Dorsey, Zuhair K Ballas, Francisco A Bonilla, Hans D. OchsAbstract:X-Linked Agammaglobulinemia is a primary humoral immunodeficiency characterized by hypogammaglobulinemia and increased susceptibility to infection. Although there is increased awareness of autoimmune and inflammatory complications in X-Linked Agammaglobulinemia (XLA), the spectrum of gastrointestinal manifestations has not previously been fully eXplored. We present a case report of a family with two affected patients with XLA. Given the gastrointestinal involvement of the grandfather in this family, we performed a retrospective descriptive analysis of XLA patients with reported diagnoses of GI manifestations and inflammatory bowel disease (IBD) or enteritis registered at the United States Immunodeficiency Network, a national registry of primary immunodeficiencies. In this cohort of patients with XLA, we found that up to 35% had concurrent gastrointestinal manifestations, and 10% had reported diagnoses of IBD or enteritis. The most commonly reported mutations were missense, which have been associated with a less severe XLA phenotype in the literature. The severity of symptoms were wide ranging, and management strategies were diverse and mainly eXperimental. Patients with XLA may require close monitoring with particular attention for GI manifestations including IBD and infectious enteritis. Further studies are needed to improve diagnosis and management of GI conditions in XLA patients.
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successful hematopoietic cell transplantation in a patient with X Linked Agammaglobulinemia and acute myeloid leukemia
Pediatric Blood & Cancer, 2015Co-Authors: Rolla Abuarja, Leah R Chernin, Ghada Abusin, Linda Cabral, Rachel A Egler, Troy R Torgerson, Jeffery J. Auletta, Hans D. Ochs, Jesus M Lopezguisa, Robert W. HostofferAbstract:X-Linked Agammaglobulinemia (XLA) is a primary immunodeficiency characterized by marked reduction in all classes of serum immunoglobulins and the near absence of mature CD19+ B-cells. Although malignancy has been observed in patients with XLA, we present the first reported case of acute myeloid leukemia (AML) in a patient with XLA. We also demonstrate the complete correction of the XLA phenotype following allogeneic hematopoietic cell transplantation for treatment of the patient's leukemia. Pediatr Blood Cancer 2015;62:1674–1676. © 2015 Wiley Periodicals, Inc.
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successful hematopoietic cell transplantation in a patient with X Linked Agammaglobulinemia and acute myeloid leukemia
Pediatric Blood & Cancer, 2015Co-Authors: Rolla Abuarja, Ghada Abusin, Linda Cabral, Rachel A Egler, Troy R Torgerson, Jeffery J. Auletta, Hans D. Ochs, Jesus M Lopezguisa, Leah Chernin, Robert W. HostofferAbstract:X-Linked Agammaglobulinemia (XLA) is a primary immunodeficiency characterized by marked reduction in all classes of serum immunoglobulins and the near absence of mature CD19(+) B-cells. Although malignancy has been observed in patients with XLA, we present the first reported case of acute myeloid leukemia (AML) in a patient with XLA. We also demonstrate the complete correction of the XLA phenotype following allogeneic hematopoietic cell transplantation for treatment of the patient's leukemia.
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familial hemophagocytic lymphohistiocytosis in two brothers with X Linked Agammaglobulinemia
Pediatric Blood & Cancer, 2008Co-Authors: Kris Ann P Schultz, Troy R Torgerson, Hans D. Ochs, Joseph P Neglia, Angela R Smith, Ashish KumarAbstract:Hemophagocytic lymphohistiocytosis (HLH) is often familial and is associated with high mortality. Primary (familial) HLH is known to occur in children with mutations in perforin, Munc13-4, or syntaXin 11. We describe a case series of two brothers who developed HLH in the setting of X-Linked Agammaglobulinemia (XLA, Bruton's disease) and adenovirus infection. Further studies revealed absence of Bruton's tyrosine kinase (BTK) protein eXpression and a novel BTK mutation.
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X Linked Agammaglobulinemia report on a united states registry of 201 patients
Medicine, 2006Co-Authors: Jerry A. Winkelstein, Kathleen E. Sullivan, Mary Ellen Conley, Mary C Marino, Howard M Lederman, Stacie M Jones, Wesley A Burks, Charlotte Cunninghamrundles, Hans D. OchsAbstract:X-Linked Agammaglobulinemia (XLA) is a primary immunodeficiency caused by mutations in the gene for Bruton tyrosine kinase (BTK) that result in the deficient development of B lymphocytes and hypogammaglobulinemia. Because the disorder is uncommon, no single institution has had sufficient numbers of patients to develop a comprehensive clinical picture of the disorder. Accordingly, a national registry of United States residents with XLA was established in 1999 to provide an updated clinical view of the disorder in a large cohort of patients. A total of 201 patients were registered by 66 physicians. The estimated birth rate for the 10-year period of 1988-1997 was 1/379,000. Infection was the most common initial clinical presentation (85%), followed by a positive family history (41%) and neutropenia (11%). Although the average age of diagnosis was younger in patients with a positive family history (mean, 2.59 yr) than in patients with a negative family history (mean, 5.37 yr) (p < 0.001), only 34.5% of patients with a positive family history at the time of their birth were diagnosed before clinical symptoms developed-that is, based on family history alone. Seventy percent of patients had at least 1 episode of otitis, 62% at least 1 episode of pneumonia, 60% at least 1 episode of sinusitis, 23% at least 1 episode of chronic/recurrent diarrhea, 21% at least 1 episode of conjunctivitis, 18% at least 1 episode of pyoderma and/or cellulitis, 11% at least 1 episode of meningitis/encephalitis, 10% at least 1 episode of sepsis, 8% at least 1 episode of septic arthritis, 6% at least 1 episode of hepatitis, and 3% at least 1 episode of osteomyelitis. Fourteen of 201 (6.9%) patients were dead at the time they were entered in the Registry. However, in a prospective 4 /4-year follow-up of living patients, only 3/80 (3.75%) patients died. Causes of death included disseminated enterovirus infection (n = 6), pulmonary insufficiency (n = 5), adenovirus infection (n = 1), sepsis (n = 1), acquired immunodeficiency disease syndrome (AIDS) (n = 1), myocarditis (n = 1), hepatitis (n = 2), and stem cell transplantation (n = 1).
Mary Ellen Conley - One of the best experts on this subject based on the ideXlab platform.
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Successful approach to treatment of Helicobacter bilis infection in X-Linked Agammaglobulinemia.
Journal of Clinical Immunology, 2012Co-Authors: Stuart E. Turvey, Annette Boos, Gregory D. Deans, Christof Senger, Julie S Prendiville, Mary Ellen Conley, Richard I. Crawford, Peter Tilley, Anne K. JunkerAbstract:Helicobacter bilis, an unusual cause of chronic infections in patients with X-Linked Agammaglobulinemia (XLA), is notoriously difficult to diagnose and eradicate. Based on the limited number of cases reported worldwide, we highlight the typical features of H. bilis infection in XLA and provide a rational and successful approach to diagnosis and treatment of this challenging infection.
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Membranous Glomerulopathy in an Adult Patient with X-Linked Agammaglobulinemia Receiving Intravenous Gammaglobulin
Journal of Investigational Allergology and Clinical Immunology, 2011Co-Authors: L.m. Endo, Jv Giannobile, Ak Dobbs, Mary Ellen Conley, Jeremy B Foote, Ewa Szymanska, William J. Cook, David G Warnock, Harry W SchroederAbstract:Abstract Background: Immune compleX deposition in the subepithelial zone of glomerular capillaries can lead to membranous glomerulopathy. Objective: To present the case of a 23-year-old man with X-Linked Agammaglobulinemia (XLA) who developed idiopathic membranous glomerulopathy while receiving intravenous immunoglobulin (IVIG). Methods: We performed an immunological workup, genetic testing, and a renal biopsy. Results: XLA was confi rmed with less than 0.02% CD19 + cells in the blood after sequence analysis revealed a nonfunctional BTK gene. The patient presented with microhematuria, which persisted for 3 years and spanned treatment with 5 different preparations of intravenous gammaglobulin. Immunohistochemistry revealed membranous glomerulopathy. Conclusion: Although endogenous serum immunoglobulin (Ig) production is severely impaired in XLA, rare B lymphocytes that have managed to mature can produce functional IgG antibodies. The pathogenic immune compleXes could refl ect IVIG reacting with polym orphic autoantigens, an endogenous IgG-producing clone reacting with a common idiotype present in the IVIG, or both.Key words: X-Linked Agammaglobulinemia (XLA). Bruton Agammaglobulinemia. Membranous glomerulopathy. Microhematuria. Intravenous gammaglobulin.■
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X Linked Agammaglobulinemia report on a united states registry of 201 patients
Medicine, 2006Co-Authors: Jerry A. Winkelstein, Kathleen E. Sullivan, Mary Ellen Conley, Mary C Marino, Howard M Lederman, Stacie M Jones, Wesley A Burks, Charlotte Cunninghamrundles, Hans D. OchsAbstract:X-Linked Agammaglobulinemia (XLA) is a primary immunodeficiency caused by mutations in the gene for Bruton tyrosine kinase (BTK) that result in the deficient development of B lymphocytes and hypogammaglobulinemia. Because the disorder is uncommon, no single institution has had sufficient numbers of patients to develop a comprehensive clinical picture of the disorder. Accordingly, a national registry of United States residents with XLA was established in 1999 to provide an updated clinical view of the disorder in a large cohort of patients. A total of 201 patients were registered by 66 physicians. The estimated birth rate for the 10-year period of 1988-1997 was 1/379,000. Infection was the most common initial clinical presentation (85%), followed by a positive family history (41%) and neutropenia (11%). Although the average age of diagnosis was younger in patients with a positive family history (mean, 2.59 yr) than in patients with a negative family history (mean, 5.37 yr) (p < 0.001), only 34.5% of patients with a positive family history at the time of their birth were diagnosed before clinical symptoms developed-that is, based on family history alone. Seventy percent of patients had at least 1 episode of otitis, 62% at least 1 episode of pneumonia, 60% at least 1 episode of sinusitis, 23% at least 1 episode of chronic/recurrent diarrhea, 21% at least 1 episode of conjunctivitis, 18% at least 1 episode of pyoderma and/or cellulitis, 11% at least 1 episode of meningitis/encephalitis, 10% at least 1 episode of sepsis, 8% at least 1 episode of septic arthritis, 6% at least 1 episode of hepatitis, and 3% at least 1 episode of osteomyelitis. Fourteen of 201 (6.9%) patients were dead at the time they were entered in the Registry. However, in a prospective 4 /4-year follow-up of living patients, only 3/80 (3.75%) patients died. Causes of death included disseminated enterovirus infection (n = 6), pulmonary insufficiency (n = 5), adenovirus infection (n = 1), sepsis (n = 1), acquired immunodeficiency disease syndrome (AIDS) (n = 1), myocarditis (n = 1), hepatitis (n = 2), and stem cell transplantation (n = 1).
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The health status and quality of life of adults with X-Linked Agammaglobulinemia
Clinical Immunology, 2006Co-Authors: Vanessa Howard, Jeffrey M. Greene, Savita G Pahwa, John Boyle, Jerry A. Winkelstein, Mehmet Kocak, Mary Ellen ConleyAbstract:Forty-one adults (mean age 33) with a definitive diagnosis of X-Linked Agammaglobulinemia (XLA) completed a questionnaire concerning current and past medical problems and quality of life. Thirty-siX of the 41 were working full time or were full time students; 18 had not missed any work or school due to infection in the previous year. Their quality of life was equivalent to that of the general US male population. Thirteen of the 41 reported that they had chronic lung disease, and 33 indicated that they had one or more episodes of sinusitis in the preceding year. Arthritis, diarrhea and skin infections were common but not debilitating. The 41 study subjects were more likely to have a prior family history of XLA, and they were more likely to have milder mutations in Btk, the gene responsible for XLA. These results indicate that most adults with XLA are moderately healthy and lead productive lives.
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genotype phenotype correlations in X Linked Agammaglobulinemia
Clinical Immunology, 2006Co-Authors: Arnon Broides, Mary Ellen Conley, Wenjian YangAbstract:No clear genotype/phenotype correlations have been established in patients with X-Linked Agammaglobulinemia (XLA). To determine if the specific mutation in Btk might be one of the factors that influences the severity of disease or if polymorphic variants in Tec, a cytoplasmic tyrosine kinase that might substitute for Btk, could contribute to the clinical phenotype, we eXamined the age at diagnosis, the percentage of peripheral blood B cells and the plasma IgM in a large group of patients with XLA. The results demonstrated that polymorphic variants in Tec were not correlated with phenotypic markers; however, the specific mutation in Btk did influence disease severity. Mutations that conceivably allow the production of some Btk, amino acid substitutions or splice defects that occur at conserved but not invariant sites in the splice consensus sequence were associated with older age at diagnosis, a higher percentage of B cells in the peripheral circulation and higher concentrations of plasma IgM.
Hirokazu Kanegane - One of the best experts on this subject based on the ideXlab platform.
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Helicobacter cinaedi-Associated Refractory Cellulitis in Patients with X-Linked Agammaglobulinemia
Journal of Clinical Immunology, 2020Co-Authors: Kento Inoue, Saeko Sasaki, Takahiro Yasumi, Kohsuke Imai, Takashi Kusunoki, Tomohiro Morio, Hirokazu KaneganeAbstract:X-Linked Agammaglobulinemia (XLA) is characterized by severe or recurrent infections, hypogammaglobulinemia, and circulating B cell deficiency. The frequent pathogens seen in patients with XLA include Streptococcus pneumoniae , Haemophilus influenzae , Pseudomonas aeruginosa , and enterovirus as well as Campylobacter and Helicobacter species . Here, we describe two patients with XLA who developed cellulitis and bacteremia caused by Helicobacter cinaedi even when administered an appropriate immunoglobulin replacement therapy. H. cinaedi may be difficult to isolate using a conventional blood culture system and could be identified by sequence analysis and mass spectrometry. H. cinaedi infection causes recurrent symptoms frequently, and patients require a long course of antibiotic treatment. Recently, the case of non- H. pylori Helicobacter (NHPH) infection such as H. cinaedi and H. bilis infection is increasing in number in patients with XLA. Systemic NHPH infection should be suspected, and eXtensive microbiological analysis should be performed to appropriately treat patients with XLA who present with fever and skin lesions.
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X-Linked Agammaglobulinemia Associated with B-Precursor Acute Lymphoblastic Leukemia
Journal of Clinical Immunology, 2015Co-Authors: Akihiro Hoshino, Yusuke Okuno, Masahiro Migita, Xi Yang, Nobutaka Kiyokawa, Yuichi Adachi, Seiji Kojima, Osamu Ohara, Hirokazu KaneganeAbstract:X-Linked Agammaglobulinemia (XLA) is clinically characterized by reduced number of peripheral B cells and diminished levels of serum immunoglobulins, and caused by a mutation in the Bruton ’ s tyrosine kinase ( BTK ) gene, which play a pivotal role in signal transduction of pre-B-cell receptor (BCR) and BCR. B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is the most common malignancy in children, and it may be associated with gene alterations that regulate B-cell development. Here we described a first case of XLA associated BCP-ALL. The whole-eXome sequencing revealed a somatic mutation in MLL2 in the sample from the onset of BCP-ALL. This study suggests that the alterations of BTK and MLL2 synergistically function as leukemogenesis.
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Pneumocystis jiroveci pneumonia as an atypical presentation of X-Linked Agammaglobulinemia.
International Journal of Hematology, 2009Co-Authors: Hirokazu Kanegane, Yoshiki Shimono, Takashi Nakano, Meina Zhao, Toshio MiyawakiAbstract:X-Linked Agammaglobulinemia (XLA) is usually presented with clinical manifestations of bacterial respiratory and/or gastrointestinal infections below the age of 1 year, when the maternal IgG through placenta disappears from the circulation of the baby. Here, we describe an infant with XLA, who presented with interstitial pneumonia suggestive of Pneumocystis jiroveci (formerly Pneumocystis carinii) infection.
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Mutation of the BTK Gene and Clinical Feature of X-Linked Agammaglobulinemia in Mainland China
Journal of Clinical Immunology, 2008Co-Authors: Ying Wang, Shunying Zhao, Yeheng Yu, Hirokazu Kanegane, Xiaochuan Wang, Qian Zhang, Jingyi Wang, Toshio MiyawakiAbstract:Introduction X-Linked Agammaglobulinemia is a prototypical humoral immunodeficiency with the mutation of the Bruton’s tyrosine kinase gene.
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toll like receptor signaling is impaired in dendritic cells from patients with X Linked Agammaglobulinemia
Clinical Immunology, 2008Co-Authors: Hiromichi Taneichi, Mostafa Mohamed Sira, Masahiro Sako, Hirokazu Kanegane, Takeshi Futatani, Kazunaga Agematsu, Naomi Kondo, Hideo Kaneko, Tsuneyasu Kaisho, Toshio MiyawakiAbstract:Abstract Bruton's tyrosine kinase (BTK), which is defective in patients with X-Linked Agammaglobulinemia (XLA), is eXpressed not only in B cells but also in monocytes and dendritic cells (DCs). DCs play a crucial role in the innate immune response against infections by sensing pathogens through Toll-like receptors (TLRs). However, it is not known whether BTK deficiency in XLA might impair TLR-mediated signaling in DCs, which are susceptible to various infections. The phenotypic maturation and cytokine production mediated by TLRs were eXamined in monocyte-derived DC from XLA patients and normal controls. The TLR eXpression in DCs was analyzed by flow cytometry. TLR-mediated signaling in DCs was evaluated for the phenotypic maturation based on CD83 eXpression and production of cytokines, such as TNF-α, IL-6 and IL-12p70. TLR levels in DCs were similar between XLA and controls. TLR2, TLR4 and TLR7/8 ligands elicited less phenotypic maturation of DCs from XLA patients than normal controls based on CD83 eXpression. Stimulation with TLR2, TLR4 and TLR7/8 ligands, as well as TLR3 ligand, resulted in significantly lower production of TNF-α, but neither IL-6 nor IL-12p70, by DCs from XLA patients in comparison to normal controls. These findings suggest that BTK may thus be required for TLR signaling in DCs. The impaired TLR signaling in DCs may therefore be partly responsible for the occurrence of severe infections with bacteria and some viruses in XLA patients.
Toshio Miyawaki - One of the best experts on this subject based on the ideXlab platform.
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Pneumocystis jiroveci pneumonia as an atypical presentation of X-Linked Agammaglobulinemia.
International Journal of Hematology, 2009Co-Authors: Hirokazu Kanegane, Yoshiki Shimono, Takashi Nakano, Meina Zhao, Toshio MiyawakiAbstract:X-Linked Agammaglobulinemia (XLA) is usually presented with clinical manifestations of bacterial respiratory and/or gastrointestinal infections below the age of 1 year, when the maternal IgG through placenta disappears from the circulation of the baby. Here, we describe an infant with XLA, who presented with interstitial pneumonia suggestive of Pneumocystis jiroveci (formerly Pneumocystis carinii) infection.
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Mutation of the BTK Gene and Clinical Feature of X-Linked Agammaglobulinemia in Mainland China
Journal of Clinical Immunology, 2008Co-Authors: Ying Wang, Shunying Zhao, Yeheng Yu, Hirokazu Kanegane, Xiaochuan Wang, Qian Zhang, Jingyi Wang, Toshio MiyawakiAbstract:Introduction X-Linked Agammaglobulinemia is a prototypical humoral immunodeficiency with the mutation of the Bruton’s tyrosine kinase gene.
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toll like receptor signaling is impaired in dendritic cells from patients with X Linked Agammaglobulinemia
Clinical Immunology, 2008Co-Authors: Hiromichi Taneichi, Mostafa Mohamed Sira, Masahiro Sako, Hirokazu Kanegane, Takeshi Futatani, Kazunaga Agematsu, Naomi Kondo, Hideo Kaneko, Tsuneyasu Kaisho, Toshio MiyawakiAbstract:Abstract Bruton's tyrosine kinase (BTK), which is defective in patients with X-Linked Agammaglobulinemia (XLA), is eXpressed not only in B cells but also in monocytes and dendritic cells (DCs). DCs play a crucial role in the innate immune response against infections by sensing pathogens through Toll-like receptors (TLRs). However, it is not known whether BTK deficiency in XLA might impair TLR-mediated signaling in DCs, which are susceptible to various infections. The phenotypic maturation and cytokine production mediated by TLRs were eXamined in monocyte-derived DC from XLA patients and normal controls. The TLR eXpression in DCs was analyzed by flow cytometry. TLR-mediated signaling in DCs was evaluated for the phenotypic maturation based on CD83 eXpression and production of cytokines, such as TNF-α, IL-6 and IL-12p70. TLR levels in DCs were similar between XLA and controls. TLR2, TLR4 and TLR7/8 ligands elicited less phenotypic maturation of DCs from XLA patients than normal controls based on CD83 eXpression. Stimulation with TLR2, TLR4 and TLR7/8 ligands, as well as TLR3 ligand, resulted in significantly lower production of TNF-α, but neither IL-6 nor IL-12p70, by DCs from XLA patients in comparison to normal controls. These findings suggest that BTK may thus be required for TLR signaling in DCs. The impaired TLR signaling in DCs may therefore be partly responsible for the occurrence of severe infections with bacteria and some viruses in XLA patients.
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relapsing campylobacter coli bacteremia with reactive arthritis in a patient with X Linked Agammaglobulinemia
Internal Medicine, 2007Co-Authors: Ayako Arai, Hirokazu Kanegane, Toshio Miyawaki, Asako Kitano, Etsuko Sawabe, Osamu MiuraAbstract:A patient genetically diagnosed with X-Linked Agammaglobulinemia repeatedly developed bacteremia due to Campylobacter coli (C. coli) for one year and seven months in spite of immunoglobulin replacement therapy. Throughout the clinical course, C. coli with identical genetic patterns was repeatedly isolated from both blood and stool cultures, thus indicating that the patient had latent intestinal infection. The bacteremia was always accompanied by reactive arthritis. Since the immunoglobulin level was eXtremely low with severe B cell deficiency, the reactive arthritis must have been induced in a humoral immunity-independent manner. Adding oral minocycline following intravenous meropenem was very effective; the stool cultures became negative and the patient has been well for more than one year without relapse of bacteremia.
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Membranoproliferative glomerulonephritis in a patient with X-Linked Agammaglobulinemia
Pediatric Nephrology, 2005Co-Authors: Atsunori Yoshino, Hiroyoshi Matsukura, Yasuki Katada, Hirokazu Kanegane, Yoshihiko Ueda, Toshio Miyawaki, Masataka Honda, Satoru Sakazume, Kazuo Obata, Toshiro NagaiAbstract:Immune compleX and complement systems play an important role in membranoproliferative glomerulonephritis (MPGN). X-Linked Agammaglobulinemia (XLA) is a primary immunodeficiency characterized by severe hypogammaglobulinemia. We report the case of an XLA patient who developed MPGN during an intravenous immunoglobulin (IVIG) treatment. In this patient, the serum IgG level was maintained at more than 400 mg/dl of regular IVIG administration (2.5 g/dose/month). The patient presented with microscopic hematuria, proteinuria (U-pro/Cr: 4.0–4.2) and low serum complement levels (C3: 57.8 mg/dl) 3 years after IVIG treatment and was diagnosed histopathologically as having MPGN type III. Both hematuria and proteinuria significantly improved, and the serum complement level returned to a normal level following methylprednisolone pulse therapy. To our knowledge, this is the first case report of MPGN associated with XLA. Although it is unclear how MPGN occurred in this XLA patient, we suggest that residual humoral immunity in the patient could be associated with the development of MPGN.
Bernd H Belohradsky - One of the best experts on this subject based on the ideXlab platform.
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BTKbase, Mutation Database for X-Linked Agammaglobulinemia (XLA)
Nucleic Acids Research, 1998Co-Authors: Mauno Vihinen, Sau-ping Kwan, Heikki Lehväslaiho, Ilkka Lappalainen, Elke Holinski-feder, T Lester, Robert N. Haire, Alfons Meindl, Bernd H Belohradsky, Hans D. OchsAbstract:X-Linked Agammaglobulinemia (XLA) is an immunodeficiency caused by mutations in the gene coding for Bruton's Agammaglobulinemia tyrosine kinase (BTK). A database (BTKbase) of BTK mutations has been compiled and the recent update lists 225 entries from 189 unrelated families showing 148 unique molecular events. Each patient is given a unique patient identity number (PIN). Information is included regarding the phenotype including symptoms. Mutations in all the five domains of BTK have been noticed to cause the disease, the most common event being missense mutations. The mutations appear almost uniformly throughout the molecule and frequently affect CpG sites forming arginine residues. A decreased frequency of missense mutations was found in the TH, SH3 and upper lobe of the kinase domain. The putative structural implications of all the missense mutations are given in the database.
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high vs low dose immunoglobulin therapy in the long term treatment of X Linked Agammaglobulinemia
JAMA Pediatrics, 1992Co-Authors: Johannes G Liese, Uwe Wintergerst, Klaus D Tympner, Bernd H BelohradskyAbstract:The data of 29 patients with X-Linked Agammaglobulinemia, who received immunoglobulin replacement therapy between 1965 and 1990, were analyzed for dose-dependent long-term results concerning infectious complications. Patients who received high-dose intravenous immunoglobulin replacement (greater than 400 mg/kg every 3 weeks) showed a significant increase in trough serum IgG levels and a significant decrease in the incidence of pneumonias and the number of days spent in the hospital compared with patients receiving intravenous immunoglobulin low-dose (less than 200 mg/kg every 3 weeks) or intramuscular immunoglobulin (less than 100 mg/kg every 3 weeks) treatment. Improvements in therapeutic outcome were particularly evident when high-dose intravenous immunoglobulin replacement therapy was started before the age of 5 years. Bacterial meningitis, chronic pulmonary disease, and bronchiectasis occurred in the intramuscular immunoglobulin group but did not occur in either of the intravenous immunoglobulin groups. High-dose intravenous immunoglobulin therapy may have a positive impact on the clinical course and may prevent severe complications in patients with X-Linked Agammaglobulinemia.
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high vs low dose immunoglobulin therapy in the long term treatment of X Linked Agammaglobulinemia
JAMA Pediatrics, 1992Co-Authors: Johannes G Liese, Uwe Wintergerst, Klaus D Tympner, Bernd H BelohradskyAbstract:• The data of 29 patients with X-Linked Agammaglobulinemia, who received immunoglobulin replacement therapy between 1965 and 1990, were analyzed for dose-dependent long-term results concerning infectious complications. Patients who received high-dose intravenous immunoglobulin replacement (>400 mg/kg every 3 weeks) showed a significant increase in trough serum IgG levels and a significant decrease in the incidence of pneumonias and the number of days spent in the hospital compared with patients receiving intravenous immunoglobulin low-dose ( ( AJDC . 1992;146:335-339)
