| 1. |
- de Faire, Ulf, et al.
(författare)
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Low levels of IgM antibodies to phosphorylcholine predict cardiovascular disease in 60-year old men : Effects on uptake of oxidized LDL in macrophages as a potential mechanism
- 2010
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Ingår i: Journal of Autoimmunity. - : Elsevier BV. - 0896-8411 .- 1095-9157. ; 34:2, s. 73-79
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Tidskriftsartikel (refereegranskat)abstract
- Objective: We here determine the role of IgM antibodies against phosphorylcholine (anti-PC) in prediction of cardiovascular disease (CVD) and on macrophage uptake of Oxidized LDL (OxLDL). Methods: From a screening of 4232 subjects, 60-year-old (2039 men and 2193 women), 211 incident cases of CVD (myocardial infarction, ischemic stroke, or hospitalized angina pectoris) and 633 age- and sex-matched controls were identified through a 5-7 year follow-up. Serum levels of IgM anti-PC was determined by ELISA. Anti-PC was extracted from pooled human IgM and the effect of anti-PC on the uptake of OxLDL was studied by FACScan. Results: Relative risks (RR) with 95% confidence intervals (Cl) by quartiles of anti-PC levels with quartile 4 set as the reference value (RR = 1.0) and adjusted for smoking, BMI, type 11 diabetes, hypercholesterolaemia, and high blood pressure yielded an excess risk for CVD only for those within the lowest quartile of anti-PC values with an RR of 1.37 (CI 0.87-2.16). However, for men stronger associations were noted with increasing multivariately adjusted RRs from quartile 4 to quartile 1. Subjects within quartile I (values below 29.7 U/ml) had a significantly increased RR of 1.96 (Cl 1.09-3.55). Further adjustments for hsCRP gave essentially the same results. No excess risk was noted for women. Specific anti-PC could be extracted from IgM and these antibodies inhibited macrophage uptake of OxLDL Conclusions: Low IgM anti-PC could be a novel risk marker for CVD among men. One possible mechanism could be inhibition of uptake of oxLDL in macrophages.
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| 2. |
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| 3. |
- Hellmark, Thomas, et al.
(författare)
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Diagnosis and classification of Goodpastures disease (anti-GBM)
- 2014
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Ingår i: Journal of Autoimmunity. - : Elsevier. - 0896-8411 .- 1095-9157. ; 48-49, s. 108-112
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Tidskriftsartikel (refereegranskat)abstract
- Goodpastures disease or anti-glomerular basement membrane disease (anti-GBM-disease) is included among immune complex small vessel vasculitides. The definition of anti-GBM disease is a vasculitis affecting glomerular capillaries, pulmonary capillaries, or both, with GBM deposition of anti-GBM auto-antibodies. The disease is a prototype of autoimmune disease, where the patients develop auto-antibodies that bind to the basement membranes and activate the classical pathway of the complement system, which start a neutrophil dependent inflammation. The diagnosis of anti-GBM disease relies on the detection of anti-GBM antibodies in conjunction with glomerulonephritis and/or alveolitis. Overt clinical symptoms are most prominent in the glomeruli where the inflammation usually results in a severe rapidly progressive glomerulonephritis. Despite modern treatment less than one third of the patients survive with a preserved kidney function after 6 months follow-up. Frequencies vary from 0.5 to 1 cases per million inhabitants per year and there is a strong genetic linkage to HLA-DRB1*1501 and DRB1*1502. Essentially, anti-GBM disease is now a preferred term for what was earlier called Goodpastures syndrome or Goodpastures disease; anti-GBM disease is now classified as small vessel vasculitis caused by in situ immune complex formation; the diagnosis relies on the detection of anti-GBM in tissues or circulation in conjunction with alveolar or glomerular disease; therapy is effective only when detected at an early stage, making a high degree of awareness necessary to find these rare cases; 20-35% have anti-GBM and MPO-ANCA simultaneously, which necessitates testing for anti-GBM whenever acute test for ANCA is ordered in patients with renal disease.
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| 4. |
- Hemminki, Kari, et al.
(författare)
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The epidemiology of Graves' disease: Evidence of a genetic and an environmental contribution.
- 2010
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Ingår i: Journal of Autoimmunity. - : Elsevier BV. - 0896-8411 .- 1095-9157. ; 34, s. 307-313
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Tidskriftsartikel (refereegranskat)abstract
- Previous family and twin studies have indicated that Graves' disease has a heritable component. Family studies have also shown that some autoimmune disease cluster in families and genetic studies have been able to show shared susceptibility genes. In the present nation-wide study we describe familial risk for Graves' disease among parents and offspring, singleton siblings, twins and spouses with regard to age of onset, gender and number and type of affected family members. Additionally familial association of Graves' disease with any of 33 other autoimmune and related conditions was analyzed. The Swedish Multigeneration Register on 0-75-year-old subjects was linked to the Hospital Discharge Register from years 1987-2007. Standardized incidence ratios (SIRs) were calculated for individuals whose relatives were hospitalized for Graves' disease compared to those whose relatives were unaffected. The total number of hospitalized Graves' patients was 15,743. Offspring with an affected family member constituted 3.6% of all patients among offspring. The familial SIR was 5.04 for individuals whose sibling was affected but it increased to 310 when two or more siblings were affected; the SIR in twins was 16.45. Familial risks were higher for males than for females. The SIR was increased to 6.22 or 30.20 when parental age was limited to 50 or 20 years, respectively. Graves' disease associated with 19 other autoimmune and related conditions, including Addison's disease, type 1 diabetes mellitus, Hashimoto/hypothyroidism, pernicious anemia, polymyositis/dermatomyositis, myasthenia gravis, discoid lupus erythematosus and localized scleroderma. Remarkably, there was a high disease concordance of 2.75 between spouses. The clustering between spouses suggests environmental effects on Graves' disease which may contribute to the observed gender effects. The demonstrated high risks should be considered in clinical counseling and in prevention plans.
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| 6. |
- Lind, Alexander, et al.
(författare)
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A/H1N1 antibodies and TRIB2 autoantibodies in narcolepsy patients diagnosed in conjunction with the Pandemrix vaccination campaign in Sweden 2009-2010.
- 2014
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Ingår i: Journal of Autoimmunity. - : Elsevier BV. - 0896-8411 .- 1095-9157. ; 50:Jan 28, s. 99-106
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Tidskriftsartikel (refereegranskat)abstract
- Narcolepsy is a lifelong sleep disorder related to hypocretin deficiency resulting from a specific loss of hypocretin-producing neurons in the lateral hypothalamic area. The disease is thought to be autoimmune due to a strong association with HLA-DQB1*06:02. In 2009 the World Health Organization (WHO) declared the H1N1 2009 flu pandemic (A/H1N1PDM09). In response to this, the Swedish vaccination campaign began in October of the same year, using the influenza vaccine Pandemrix(®). A few months later an excess of narcolepsy cases was observed. It is still unclear to what extent the vaccination campaign affected humoral autoimmunity associated with narcolepsy. We studied 47 patients with narcolepsy (6-69 years of age) and 80 healthy controls (3-61 years of age) selected after the Pandemrix vaccination campaign. The first aim was to determine antibodies against A/H1N1 and autoantibodies to Tribbles homolog 2 (TRIB2), a narcolepsy autoantigen candidate as well as to GAD65 and IA-2 as disease specificity controls. The second aim was to test if levels and frequencies of these antibodies and autoantibodies were associated with HLA-DQB1*06:02. In vitro transcribed and translated [(35)S]-methionine and -cysteine-labeled influenza A virus (A/California/04/2009/(H1N1)) segment 4 hemagglutinin was used to detect antibodies in a radiobinding assay. Autoantibodies to TRIB2, GAD65 and IA-2 were similarly detected in standard radiobinding assays. The narcolepsy patients had higher median levels of A/H1N1 antibodies than the controls (p = 0.006). A/H1N1 antibody levels were higher among the <13 years old (n = 12) compared to patients who were older than 30 years (n = 12, p = 0.014). Being HLA-DQB1*06:02 positive was associated with higher A/H1N1 antibody levels in both patients and controls (p = 0.026). Serum autoantibody levels to TRIB2 were low overall and high binders did not differ between patients and controls. We observed an association between levels of A/H1N1 antibodies and TRIB2 autoantibody levels particularly among the youngest narcolepsy patients (r = 0.819, p < 0.001). In conclusion, following the 2009 influenza pandemic vaccination, A/H1N1 antibody levels were associated with young age-at-onset narcolepsy patients positive for HLA-DQB1*06:02. The possibility that TRIB2 is an autoantigen in narcolepsy remains to be clarified. We could verify autoantibody responses against TRIB2 which needs to be determined in larger patient cohorts and control populations.
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| 7. |
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| 8. |
- Lindh, Emma, et al.
(författare)
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Autoimmunity and cystatin SA1 deficiency behind chronic mucocutaneous candidiasis in autoimmune polyendocrine syndrome type 1
- 2013
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Ingår i: Journal of Autoimmunity. - : Elsevier BV. - 0896-8411 .- 1095-9157. ; 42, s. 1-6
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Tidskriftsartikel (refereegranskat)abstract
- Patients with the monogenic disease autoimmune polyendocrine syndrome type I (APSI) develop autoimmunity against multiple endocrine organs and suffer from chronic mucocutaneous candidiasis (CMC), a paradoxical complication with an unknown mechanism. We report here that saliva from APSI patients with CMC is defective in inhibiting growth of Candida albicans in vitro and show reduced levels of a salivary protein identified as cystatin SA1. In contrast, APSI patients without CMC express salivary cystatin SA1 and can inhibit C. albicans to the same extent as healthy controls. We evaluated the anti-fungal activity of cystatin SA1 and found that synthesized full length cystatin SA1 efficiently inhibits growth of C. albicans in vitro. Moreover, APSI patients exhibit salivary IgA autoantibodies recognizing myosin-9, a protein expressed in the salivary glands, thus linking autoimmunity to cystatin SA1 deficiency and CMC. This data suggests an autoimmune mechanism behind CMC in APSI and provides rationale for evaluating cystatin SA1 in antifungal therapy.
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