| 1. |
- Alper, CA, et al.
(författare)
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Immunoglobulin deficiencies and susceptibility to infection among homozygotes and heterozygotes for C2 deficiency
- 2003
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Ingår i: Journal of Clinical Immunology. - 0271-9142. ; 23:4, s. 297-305
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Tidskriftsartikel (refereegranskat)abstract
- About 25% of C2-deficient homozygotes have increased susceptibility to severe bacterial infections. C2-deficient homozygotes had significantly lower serum levels of IgG2, IgG4, IgD, and Factor B, significantly higher levels of IgA and IgG3 and levels of IgG1 and IgM similar to controls. Type I ( 28 bp deletion in C2 exon 6 on the [HLA-B18, S042, DR2] haplotype or its fragments) and type II ( non-type I) C2-deficient patients with increased susceptibility to bacterial infection had significantly lower mean levels of IgG4 ( p < 0.04) and IgA ( p < 0.01) than those without infections ( who had a higher than normal mean IgA level) but similar mean levels of other immunoglobulins and Factor B. Of 13 C2-deficient homozygotes with infections, 85% had IgG4 deficiency, compared with 64% of 25 without infections. IgD deficiency was equally extraordinarily common among infection-prone (50%) and noninfection-prone (70%) homozygous type I C2-deficient patients. IgD deficiency was also common (35%) among 31 type I C2-deficient heterozygotes ( with normal or type II haplotypes), but was not found in 5 type II C2-deficient heterozygotes or 1 homozygote. Thus, C2 deficiency itself is associated with many abnormalities in serum immunoglobulin levels, some of which, such as in IgG4 and IgA, may contribute to increased susceptibility to infection. In contrast, IgD deficiency appears not to contribute to increased infections and appears to be a dominant trait determined by a gene or genes on the extended major histocompatibility complex (MHC) haplotype [HLA-B18, S042, DR2] ( but probably not on type II C2-deficient haplotypes) similar to those previously identified on [HLA-B8, SC01, DR3] and [HLA-B18, F1C30, DR3].
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| 2. |
- C Kapetanovic, Meliha, et al.
(författare)
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Influence of methotrexate, TNF blockers and prednisolone on antibody responses to pneumococcal polysaccharide vaccine in patients with rheumatoid arthritis.
- 2006
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Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 45:1, s. 106-111
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To compare antibody responses to 23-valent pneumococcal vaccine (Pneumovax (R)) in controls and patients with established rheumatoid arthritis (RA) treated with TNF blockers, methotrexate (MTX) or a combination of both. Methods. Patients with RA (n = 149) and healthy controls (n = 47) were vaccinated. Treatment with TNF blockers (etanercept or infliximab) and MTX was given to 50 patients, and 62 patients were treated with TNF blockers alone or with other DMARDs. MTX alone was given to 37 patients. Concentrations of immunoglobulin G (IgG) antibodies against pneumococcal capsular polysaccharides 23F and 6B were measured by enzyme-linked immunoassay before and 4-6 weeks after vaccination. An immune response was defined as a twofold or higher increase in antibody concentration following vaccination. Results. Prevaccination antibody levels for both 23F and 6B were similar in the patient groups. Antibody concentrations after vaccination increased significantly in all groups. Patients treated with TNF blockers without MTX showed better immune responses than those treated with TNF blockers in combination with MTX (P = 0.037 for 23F and P = 0.004 for 6B) or MTX alone (P < 0.001 for both 23F and 6B). RA patients given MTX alone had the lowest immune responses. Prednisolone treatment did not influence the responses. Conclusions. Patients treated with TNF blockers and controls showed similar responses to vaccination. In contrast, patients treated with MTX had reduced responses regardless of anti-TNF treatment. The findings do not argue against the use of pneumococcal vaccination in RA patients undergoing treatment with TNF blockers.
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| 3. |
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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. |
- Ingvarsson, Johan, et al.
(författare)
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Design of recombinant antibody microarrays for serum protein profiling: Targeting of complement proteins
- 2007
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 6:9, s. 3527-3536
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Tidskriftsartikel (refereegranskat)abstract
- Antibody-based microarrays is a novel technology with great promise for high-throughput proteomics. The process of designing high-performing arrays has, however, turned out to be challenging. Here, we have designed the next generation of a human recombinant scFv antibody microarray platform for protein expression profiling of nonfractionated biotinylated human plasma and serum proteomes. The setup, based on black polymer Maxisorb slides interfaced with a fluorescent-based read-out system, was found to provide specific, sensitive (subpicomolar (pM) range) and reproducible means for protein profiling. Further, a chip-to-chip normalization protocol critical for comparing data generated on different chips was devised. Finally, the microarray data were found to correlate well with clinical laboratory data obtained using conventional methods, as demonstrated for a set of medium abundant (micromolar (mu M) to nanomolar (nM) range) protein analytes in serum and plasma samples derived from healthy and complement-deficient individuals.
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| 7. |
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| 8. |
- Jönsson, Göran, et al.
(författare)
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Homozygosity for the IgG2 subclass allotype G2M(n) protects against severe infection in hereditary C2 deficiency
- 2006
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Ingår i: Journal of Immunology. - 1550-6606. ; 177:1, s. 722-728
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Tidskriftsartikel (refereegranskat)abstract
- Homozygous C2 deficiency (C2D) is the most common deficiency of the classical complement pathway in Western countries. It is mostly found in patients with autoimmune disease or susceptibility to bacterial infections and in healthy persons. We wished to assess to what extent other immunological factors might explain differences of susceptibility to infections in C2D. For this reason, 44 Swedish patients with C2D were stratified with regard to the severity of documented infections. Investigations of IgG subclass levels, IgG subclass-specific GM allotypes, concentrations of factor B, properdin, and factor H, and polymorphisms of mannan-binding lectin and the Fe receptors Fc gamma RIIa and Fc gamma RIIIb were performed. Homozygosity for the G2M*n allele, which is known to promote Ab responses to polysaccharide Ags, was strongly associated with the absence of severe infections (P < 0.001) in the patients, suggesting a major protective role. The combination of mannan (or mannose)-binding lectin and C2 deficiency was found to be a minor susceptibility factor for invasive infection (p = 0.03). Low concentrations of IgG2 and factor B might sometimes contribute to susceptibility to infection. Other factors investigated did not appear to be important. In conclusion, the findings indicated that efficient Ab responses to polysaccharides are protective against severe infection in C2D. Implications with regard to vaccinations should be considered.
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| 9. |
- Jönsson, Göran, et al.
(författare)
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Rheumatological manifestations, organ damage and autoimmunity in hereditary C2 deficiency.
- 2007
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Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 46:7, s. 1133-1139
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To analyse rheurnatological manifestations, organ damage and autoimmune responses in a large cohort of patients (n = 45) with homozygous C2 deficiency (C2D) and long-term follow-up. Methods. Medical records were reviewed and were supplemented with a mailed questionnaire for assessment of cardiovascular disease (CVD) risk factors. Organ damage was evaluated using the Systemic Lupus International Collaborative Clinics/American College of Rheumatology Damage Index (SLICC/ACR DI). Causes for disability pensions were investigated. Autoantibodies were determined with established methods. Results. Patients with rheurnatological diseases had systemic lupus erythematosus (SLE, n = 12), undifferentiated connective tissue disease (n=5) or vasculitis (n=3). Judging from annual SLICC/ACR DI, C2D patients with SLE run a similar risk of development of severe disease as other patients with SLE. An increased rate of CVD was observed not explained by Framingham-related risk factors. Disability pensions were mainly related to rheurnatological disease. The prevalence of anti-nuclear antibodies in C2D with SLE and of anti-SS-A was 25% while anti-RNP was found in 45%. Only one patient showed antibodies to dsDNA. Formation of anti-cardiolipin antibodies (aCL) appeared to be increased in C2D despite the absence of an anti-phosphol ipid syndrome. The prevalence of antibodies to the collagen-like region of C1q (C1qCLR) was also remarkably high and was not related to rheumatological manifestations. Conclusions. Severity of SLE in C2D is similar to that of SLE in other patients. Conventional risk factors do not explain the occurrence of CVD in C2D. The high prevalence of aCL and anti-C1qCLR indicates mechanisms through which impaired complement function promotes formation of autoantibodies.
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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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