[Autoimmune/inflammatory syndrome induced by aduvants].

For decades, breast implants have been available for breast reconstructions and breast augmentations to improve the patients' health-related quality of life. Silicone implants (SI) have been used since the middle of the last century for breast reconstruction, for example after breast cancer, for birth defects, gender confirmation procedures, or for breast augmentation. Every year, several hundred SI are performed in Iceland for these purposes, but no central register is maintained. It can be estimated that at least 1000 - 3000 women have SI in Iceland and that around 300 Icelandic patients get SI every year. This informal review article discusses the so-called ASIA syndrome, the immunological effects of silicone and the possible relationship of SI to autoimmune diseases, symptoms, and diagnosis. In the methodology, this paper does not rely on the strict conditions of systematic reviews, but the authors relied only on peer-reviewed sources through PubMed, UpToDate and Scopus. The keywords used are silicon, silicon implant, silicon particles, immune response, autoimmunity, autoinflammation, Autoimmune/inflammatory syndrome induced by aduvants, ASIA, ASIA syndrome, breast implant illness. The paper reviews known facts about the disease, its characteristics, and statistical aspects.

Lower expression levels of the programmed death 1 receptor on CD4+CD25+ T cells and correlation with the PD-1.3A genotype in patients with systemic lupus erythematosus.

OBJECTIVE: A genetic polymorphism in the programmed death 1 (PD-1) gene encoding the coinhibitory PD-1 immunoreceptor, PD-1.3A, is associated with systemic lupus erythematosus (SLE). The aim of this study was to assess PD-1 receptor expression in patients with SLE, in comparison with relatives and unrelated healthy controls, and to identify correlations of lower expression levels of PD-1 receptor with the PD-1.3A genotype. METHODS: Patients with SLE, patients' relatives, and unrelated healthy control subjects from Iceland and Sweden were studied. Peripheral blood mononuclear cells (PBMCs) were stimulated with anti-CD3/anti-CD28, and PD-1 expression was analyzed by flow cytometry. PD-1.3A/G genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: PD-1 expression on PBMCs was induced after antibody stimulation, showing increases of 2.1-fold in SLE patients, 3.1-fold in relatives, and 5.1-fold in healthy controls. The frequency of PD-1+ cells was significantly lower in SLE patients compared with relatives and healthy controls. PD-1 expression on PD-1+ cells and on CD4+CD25+ T cells was significantly lower in SLE patients and relatives compared with healthy controls. PD-1 expression was significantly elevated on CD25(high) cells. Levels of PD-1 expression on CD25(high) and CD25(intermediate) cells were significantly lower in SLE patients compared with healthy controls. PD-1 was expressed on both FoxP3- and FoxP3+ cells. Lower expression of PD-1 was significantly correlated with the PD-1.3A/G genotype. CONCLUSION: The results demonstrate significantly lower PD-1 receptor expression in SLE patients and their relatives and reveal a significant correlation of lower PD-1 expression with the PD-1.3A allele. Thus, PD-1.3A may contribute to abnormalities in PD-1 receptor expression on CD4+CD25+ T cells in patients with SLE, providing support for an important role of the PD-1 pathway in SLE and, possibly, in other autoimmune diseases.

Association of three systemic lupus erythematosus susceptibility factors, PD-1.3A, C4AQ0, and low levels of mannan-binding lectin, with autoimmune manifestations in Icelandic multicase systemic lupus erythematosus families.

OBJECTIVE: To study autoimmune diseases and autoantibodies in Icelandic multicase systemic lupus erythematosus (SLE) families and to determine the association of 3 SLE susceptibility factors, PD-1.3A, C4AQ0, and low levels of mannan-binding lectin (MBL), with autoimmune disease in this population. METHODS: Eight SLE multicase families were studied, comprising a total of 124 family members (23 patients with SLE and 101 relatives). The diagnosis of an autoimmune disease was established and autoantibodies were measured in each family. In addition, PD-1.3A alleles were genotyped, and C4AQ0 allotypes were established by electrophoresis and haplotype analysis. Low levels of MBL were determined using enzyme-linked immunosorbent assay and variant-allele genotyping. RESULTS: In the SLE multicase families there was a high frequency of other autoimmune diseases (32.2%) and a high frequency of autoantibodies (53.2%). Of all family members, 59.7% were determined to have SLE, other autoimmune diseases, antinuclear antibodies, and/or other autoantibodies. The families showed genetic heterogeneity for PD-1.3A, C4AQ0, and low MBL levels; the frequency of each factor ranged from 0% to 85%. The frequencies of PD-1.3A and C4AQ0 were significantly increased in patients with SLE, relatives with other autoimmune diseases, and non-autoimmune disease relatives compared with controls. In the 7 families whose members had low levels of MBL, this factor was significantly associated with SLE, but the frequency of low MBL was decreased in relatives with other autoimmune diseases as compared with non-autoimmune disease relatives and controls. There were indications of an additive effect, and 91% of patients with SLE, 78% of relatives with other autoimmune diseases, and 75% of non-autoimmune disease relatives carried at least 1 of the 3 factors. CONCLUSION: These results demonstrate a high frequency of autoimmune diseases and autoantibodies in SLE multicase families. PD-1.3A and C4AQ0 are part of a predisposing genetic background. Other genetic and/or environmental factors are necessary for disease expression, demonstrated by a high frequency of PD-1.3A and C4AQ0 in non-autoimmune disease relatives. Low MBL levels may be one such contributing factor. The results of this study provide an example of epistatic genetic effects and overlapping genetics in autoimmune diseases.

C4A deficiency and elevated level of immune complexes: the mechanism behind increased susceptibility to systemic lupus erythematosus.

OBJECTIVE: Studies of an Icelandic cohort showed that susceptibility to systemic lupus erythematosus (SLE) in individuals with C4A deficiency was increased only in the presence of increased concentrations of immune complexes. We investigated the interaction of C4A deficiency with elevated concentrations of immune complexes in healthy individuals; i.e., how different levels of C4A affected the activation of C4 and C3 and subsequent binding of increased immune complex load to human red blood cells (RBC). METHODS: Forty-five healthy individuals having different levels of C4A were studied, 8 with homozygous C4AQ0, 12 with heterozygous C4A deficiency, and 25 with normal C4A. For comparison to the complement status present after prolonged disease activity, 5 patients with SLE homozygous for C4AQ0 were also studied. RESULTS: The results showed that intact immune complex-RBC binding is dependent on the levels of immune complex-bound C3 fragments, which correlate to the levels of IC-bound C4Ad (R = 0.677, p = 0.02), but not on levels of IC-bound total C4d (R = 0.451, p = 0.16). Immune complex binding to RBC was also evaluated in increasing immune complex load. C4A deficient sera had less ability to bind the increased immune complex load to RBC than sera with normal C4A. These results are consistent with the presence of increased amounts of poorly opsonized immune complexes in C4A deficiency, leading to increased precipitation in tissues and initiation of a self-perpetuating cycle. CONCLUSION: Susceptibility to SLE is increased in individuals with C4A deficiency as C3 opsonization of immune complexes becomes insufficient at elevated immune complex concentrations.