| 1. |
- Berglund, Åke, et al.
(författare)
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The response to vaccination against influenza A(H1N1) 2009, seasonal influenza and Streptococcus pneumoniae in adult outpatients with ongoing treatment for cancer with and without rituximab
- 2014
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Ingår i: Acta Oncologica. - : Taylor & Francis Group. - 0284-186X .- 1651-226X. ; 53:9, s. 1212-1220
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Tidskriftsartikel (refereegranskat)abstract
- It is debated whether cancer patients treated with chemotherapy can mount an adequate response to vaccination.Material and methods: Ninety-six adult outpatients with cancer, who were undergoing chemotherapy and/or monoclonal antibody, tyrosine kinase inhibitor, irradiation or corticosteroid treatments, were studied. Two doses of the pandemic infl uenza A(H1N1)/09 AS03-adjuvanted split virion vaccine, one dose of the seasonal infl uenza vaccine and one dose of the 23-valent pneumococcal polysaccharide vaccine were given. Serum haemagglutination inhibition (HI) assays were used to determine antibody titres against the infl uenza strains. For the pneumococcal vaccine 14 different serotypespecifi c anti-capsular antibodies were measured by bead assay xMAP ® .Results: Patients treated with rituximab did not respond to vaccination. For patients without rituximab treatment 4% had putatively protective antibodies before vaccination (HI 40) to the pandemic-like strain A/California7/2009HINI. After the fi rst and second dose of vaccine, seroprotection rates (SPR) were 62% and 87%, and seroconversion rates (SCR) 62% and 84%, respectively. Before seasonal fl u vaccination SPR against infl uenza A/Brisbane/59/2007H1N1 and A/Uruguay/10/2007H3N2 were 19% and 17%, respectively. After vaccination, SPR were 70% and 59% and SCR 42% and 50%, respectively. For the pneumococcal vaccine protective antibodies were found to 40% of the 14 strains before and to 68% after vaccination. The mean response to pneumococcal vaccination was to 44% of the 14 serotypes. A response to at least 50% of the 14 serotypes was found in 49% of the patients. No serious adverse events were reported.Conclusion: A substantial number of adult cancer patients with ongoing chemotherapy treatment could mount an adequate serological response to infl uenza and pneumococcal vaccination without severe adverse events. Thus, vaccination should be recommended. Adjuvanted vaccines may improve the vaccine response among this patient group. Patients recently treated with rituximab do not respond to vaccination.
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| 2. |
- Brodszki, Nicholas, et al.
(författare)
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Immune responses following meningococcal serogroups A, C, Y and W polysaccharide vaccination in C2-deficient persons: Evidence for increased levels of serum bactericidal antibodies.
- 2015
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Ingår i: Vaccine. - : Elsevier BV. - 1873-2518 .- 0264-410X. ; 33:15, s. 1839-1845
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Tidskriftsartikel (refereegranskat)abstract
- Complement C2 deficiency (C2D) is associated with immunological diseases and increased susceptibility to invasive infections caused by encapsulated bacteria such as Neisseria menigitidis. In this study we evaluate the immunogenicity of vaccination against N. menigitidis in C2D. C2D patients (n=22) and controls (n=52) were given a tetravalent meningococcal polysaccharide vaccine. Serum bactericidal antibody (SBA) titres (serogroups A, C, Y and W) were analysed using a rabbit complement source. Levels of IgG, IgM, and IgA, factor B, and factor H, polymorphisms of MBL and Fc-gamma receptors were determined. The C2D patients responded with an increased SBA titre to all four serogroups (p<0.001). The response rates define as SBA titres ≥8 were found to be between 85.7% and 92.5%. The post-vaccination titres for serogroups C, Y and W were equal to healthy controls. C2D patients with a history of invasive infection had a lower post-vaccination SBA titres both compared to healthy C2D persons (p=0.03) and compared to controls (p<0.0001). We found that the G2M*n/G2M*n genotype were associated with a higher SBA titres after immunization (p=0.03). None of the other investigated immunological factors appear to be important in influencing the vaccine responses. Autoimmune diseases in C2D did not affect the vaccine response. In general, vaccination against meningococci gave rise to antibody responses in the C2D patients that equal healthy controls. The response rate was lower to serogroup A and among C2D patients with history of invasive infections. The presence of G2M*n/G2M*n genotype was associated with higher SBA titres after immunization.
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| 3. |
- Brodszki, Nicholas, et al.
(författare)
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Primary immunodeficiency in infection-prone children in southern Sweden: occurrence, clinical characteristics and immunological findings.
- 2014
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Ingår i: BMC Immunology. - : Springer Science and Business Media LLC. - 1471-2172. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Primary immunodeficiency diseases (PIDs) comprise a heterogeneous group of disorders mainly characterized by increased susceptibility to infections. The aims of this study were to estimate the occurrence rate of PID in the paediatric (age ≤ 18 years) population of southern Sweden (approx. 265,000 children) and to describe their demographic, clinical and immunological characteristics. During a period of 4 years, in four paediatric speciality clinics in Skåne County in southern Sweden, children being seen for infections and fulfilling specific criteria were evaluated according to a predefined examination schedule. The initial analysis consisted of complete blood counts with analysis of lymphocyte subpopulations (T, B, NK cells), measurement of immunoglobulins (IgG, IgA, IgM, IgE and IgG subclasses), and assessment of the complement system (classical, alternative and lectin pathways). In addition, results of these immunological analyses in other children from the same area and time period were evaluated.
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| 4. |
- Genel, F, et al.
(författare)
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Complement factor I deficiency associated with recurrent infections, vasculitis and immune complex glomerulonephritis
- 2005
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Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 1651-1980 .- 0036-5548. ; 37:8, s. 615-618
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Tidskriftsartikel (refereegranskat)abstract
- Here we report complement factor I deficiency in an 11-y-old girl from a consanguineous Turkish family, who presented with recurrent pyogenic infections, vasculitic eruptions and immune complex glomerulonephritis. A moderately low C3 level together with the clinical picture suggested a deficiency affecting regulation of complement activation. Analysis of haemolytic activity revealed absence of alternative pathway activity and subsequent analysis showed no detectable factor I (<2%) together with a low level of factor B and a moderately low level of factor H, indicating consumption secondary to the factor I deficiency. Factor I inhibits complement activation beyond C3 by cleavage of C3b in the presence of cofactors. Complement factor I deficiency is frequently associated with recurrent pyogenic infections mainly affecting the upper and lower respiratory tract, or presenting as meningitis or septicaemia, while rheumatic disorders have not been a prominent feature. The patient's sister also suffered from recurrent pyogenic infections and had a low C3 level clearly suggesting the same deficiency.
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| 5. |
- Genel, Ferah, et al.
(författare)
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Properdin deficiency in a boy with fulminant meningococcal septic shock
- 2006
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Ingår i: Acta Pædiatrica. - : Wiley. - 1651-2227 .- 0803-5253. ; 95:11, s. 1498-1500
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Tidskriftsartikel (refereegranskat)abstract
- Bacterial meningitis is a rare presentation for congenital immunodeficiency, but meningococcal invasive diseases and meningitis have been associated with late complement component deficiencies and properdin deficiency. A 5(1)/(2)-y-old boy of non-consanguineous parents was admitted to our hospital with meningococcal septic shock. He had previously been suffering from recurrent respiratory infections. His 13-y-old brother had also been treated for meningococcal meningitis when he was 7 y old. Immunological studies, done after recovery, on the patient and his two brothers revealed normal immunoglobulin, IgG subclasses, C3, C4 and CH50 levels. Haemolytic activity of the alternative complement pathway could not be detected, and properdin concentrations were < 0.01 mg/l in serum samples from the patient and his brothers. The patient and family members received quadrivalent polysaccharide meningococcal vaccine. The patient was discharged on penicillin prophylaxis, and he remained healthy during the ensuing year. Conclusion: Our findings stress that measurement of the haemolytic activity of the alternative complement pathway in addition to classical pathway haemolytic complement activity should be performed in patients with meningococcal disease to reveal various forms of complement deficiency. This is particularly important when there is a family history, or recurrences or infection due to uncommon serogroups. Deficient individuals and affected family members might be protected from infection by vaccination.
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| 6. |
- Gulez, N., et al.
(författare)
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Homozygosity For a Novel Mutation in the C1q C Chain Gene in a Turkish Family With Hereditary C1q Deficiency
- 2010
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Ingår i: Journal of Investigational Allergology & Clinical Immunology. - 1698-0808. ; 20:3, s. 255-258
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Tidskriftsartikel (refereegranskat)abstract
- Hereditary complete deficiency of complement component C1q is associated with a high prevalence of systemic lupus erythematosus and increased susceptibility to severe recurrent infections. An 11-year-old girl was screened for immunodeficiency due to a history of recurrent meningitis and pneumonia. Immunologic studies revealed absence of classic pathway hemolytic activity and undetectable levels of C1q. Exon-specific amplification of genomic DNA by polymerase chain reaction followed by direct sequence analysis revealed a novel homozygous missense mutation at codon 48 in the C1q C gene causing a glycine-to-arginine substitution affecting the collagen-like region of C1q. No changes were seen in the exons of the A and B chains. The mutation affected both the formation and the secretion of C1q variant molecules. We describe a novel mutation in the C1q C chain gene that leads to an interchange in amino acids resulting in absence of C1q in serum.
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| 7. |
- Hamsten, C., et al.
(författare)
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Heat differentiated complement factor profiling
- 2015
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Ingår i: Journal of Proteomics. - : Elsevier BV. - 1874-3919 .- 1876-7737. ; 126, s. 155-162
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Tidskriftsartikel (refereegranskat)abstract
- Complement components and their cascade of reactions are important defense mechanisms within both innate and adaptive immunity. Many complement deficient patients still remain undiagnosed because of a lack of high throughput screening tools. Aiming towards neonatal proteome screening for immunodeficiencies, we used a multiplex profiling approach with antibody bead arrays to measure 9 complement proteins in serum and dried blood spots. Several complement components have been described as heat sensitive, thus their heat-dependent detectability was investigated. Using sera from 16 patients with complement deficiencies and 23 controls, we confirmed that the proteins C1q, C2, C3, C6, C9 and factor H were positively affected by heating, thus the identification of deficient patients was improved when preheating samples. Measurements of C7, C8 and factor I were negatively affected by heating and non-heated samples should be used in analysis of these components. In addition, a proof of concept study demonstrated the feasibility of labeling eluates from dried blood spots to perform a subsequent correct classification of C2-deficiencies. Our study demonstrates the potential of using multiplexed single binder assays for screening of complement components that open possibilities to expand such analysis to other forms of deficiencies.
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| 8. |
- Krmar, R T, et al.
(författare)
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Acute renal failure in dense deposit disease: complete recovery after combination therapy with immunosuppressant and plasma exchange.
- 2011
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Ingår i: Clinical Nephrology. - 0301-0430. ; 75:S1, s. 4-10
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Tidskriftsartikel (refereegranskat)abstract
- We describe the clinical course of a female adolescent who was followed because of isolated microhematuria and hypocomplementemia before admission to hospital with a sudden onset of acute renal failure. At presentation, she exhibited complement consumption through the complement alternative pathway (AP) while other serologic tests were negative. Renal biopsy revealed dense deposit disease (DDD) with a crescentic pattern. Intravenous methylprednisolone, followed by plasma exchange (PE), and intravenous cyclophosphamide pulses were started shortly after admission. C3NeF and anti-factor H antibody tests were negative. Serum factor H and I levels were normal as well as factor H activity. Screening for mutation in the factor H gene revealed the H402 allele variant. Clinical remission, defined as normalization in renal function and in the activity levels of the complement AP, was noted at one month post-presentation and throughout the follow-up. A repeat renal biopsy showed the disappearance of crescent formation, whereas electron microscopy revealed no regression in dense transformation of the lamina densa. In summary, our patient was successfully treated with immunosuppressant and PE. The absence of known factors associated with DDD suggests that, in this particular case, other regulatory mechanisms of complement AP might have been involved in the disease process.
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| 9. |
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| 10. |
- Melander Skattum, Lillemor, et al.
(författare)
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Antibodies against Four Proteins from a Streptococcus pyogenes Serotype M1 Strain and Levels of Circulating Mannan-Binding Lectin in Acute Poststreptococcal Glomerulonephritis.
- 2006
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Ingår i: International Archives of Allergy and Immunology. - : S. Karger AG. - 1423-0097 .- 1018-2438. ; 140:1, s. 9-19
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Tidskriftsartikel (refereegranskat)abstract
- <i>Background:</i> Responses against antigens from the potentially nephritogenic <i>Streptococcus pyogenes</i> serotype M1 in patients with acute poststreptococcal glomerulonephritis (AGN) were studied to seek indications of expression of these antigens during the preceding infection. Also, the question was asked whether the complement protein mannan-binding lectin (MBL) is required for development of the hypocomplementemia associated with AGN. Hypothetically, the lectin pathway might trigger the alternative pathway, which is consistently activated in AGN. <i>Methods:</i> Antibodies against three proteins associated with M1, M1 protein, streptococcal inhibitor of complement (SIC) and protein H, an IgG-binding protein, were determined by ELISA in 56 children and 17 adults with AGN. Antibodies against streptococcal cysteine proteinase, which is produced by all serotypes of <i>S. pyogenes</i>, were also examined. MBL concentrations were measured in the same 71 patients by a sandwich ELISA. <i>Results:</i> Increased concentrations of antibodies were found against all four streptococcal proteins, albeit not uniformly distributed between different subgroups of patients. The prevalence of low MBL concentrations (<100 µg/l) including 2 patients with undetectable MBL (<10 µg/l) was similar in AGN (11%) and in controls (16%). <i>Conclusions:</i> Our results give evidence of exposure to SIC and protein H in conjunction with AGN. This implies that SIC and protein H and/or cross-reacting proteins may have a role in the pathogenesis of AGN or that streptococci expressing SIC or protein H are nephritogenic for other reasons. The finding of MBL-deficient individuals among the patients demonstrates that MBL is not necessary for the recruitment of complement in AGN.
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