Dataset Information

Autoantibodies Against Albumin in Patients With Systemic Lupus Erythematosus.

ABSTRACT: Objectives: Autoantibodies and aberrant immune complexes are pathological hallmarks of systemic lupus erythematosus (SLE). This study aimed to determine the occurrence of IgG autoantibodies against human serum albumin (anti-HSA IgG) and their potential association with antibodies against bovine serum albumin (anti-BSA IgG) in patients with SLE. Methods: Sera of 180 SLE patients included to the Swiss SLE Cohort Study and 188 age- and sex-matched healthy controls were evaluated. Levels of anti-HSA IgG and anti-BSA IgG were quantified by ELISA. Selected samples were further characterized using serum fractions obtained by fast liquid chromatography (FPLC). Results: SLE patients had increased levels of anti-HSA IgG (p = 0.002) but similar levels of anti-BSA IgG compared to matched healthy controls. Anti-HSA IgG levels correlated with the SLE Disease Activity Index (SLEDAI), which was more pronounced in patients with an physician's global assessment (PGA) of ? 1 (r = 0.309, p = 0.0066). Anti-HSA IgG was partially complexed with serum albumin but also occurred as monomeric autoantibodies in highly positive SLE patients. A positive correlation between anti-HSA IgG and anti-BSA IgG was found that was stronger in SLE patients than in healthy controls (r = 0.3172, p < 0.001 vs. r = 0.2122, p < 0.0035). Binding of anti-BSA IgG was inhibited partially in the presence of HSA in samples with double positivity for anti-HSA and anti-BSA (median inhibition 47.9%, range 0.9-100%) and vice versa. Conclusion: In SLE patients there is an increased prevalence of anti-HSA IgG antibodies that are associated with SLE disease activity.

SUBMITTER: Nehring J

PROVIDER: S-EPMC6176020 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Autoantibodies Against Albumin in Patients With Systemic Lupus Erythematosus.

Nehring Josephine J Schirmbeck Lucia A LA Friebus-Kardash Justa J Dubler Denise D Huynh-Do Uyen U Chizzolini Carlo C Ribi Camillo C Trendelenburg Marten M

Frontiers in immunology 20181002

<b>Objectives:</b> Autoantibodies and aberrant immune complexes are pathological hallmarks of systemic lupus erythematosus (SLE). This study aimed to determine the occurrence of IgG autoantibodies against human serum albumin (anti-HSA IgG) and their potential association with antibodies against bovine serum albumin (anti-BSA IgG) in patients with SLE. <b>Methods:</b> Sera of 180 SLE patients included to the Swiss SLE Cohort Study and 188 age- and sex-matched healthy controls were evaluated. Leve ...[more]

PMID: 30333817

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Project description:Systemic lupus erythematosus is a chronic autoimmune disease with multifactorial ethiopathogenesis. The complement system is involved in both the early and late stages of disease development and organ damage. To better understand autoantibody mediated complement consumption the GAPAID consortium examined ex vivo immune complex formation on autoantigen arrays. We recruited patients with SLE (n=211), with other systemic autoimmune diseases (n=65) and non-autoimmune control subjects (n=149) in two rheumatology tertiary care centers. Standard clinical and laboratory data were collected from all subjects and serum complement levels were determined in SLE patients. The genotype of SNP rs1143679 in the ITGAM gene was also determined. On-chip formation of immune complexes was examined using a functional immunoassay on autoantigen microarray. The amount of antigen-bound IgM, IgG and complement C4 and C3 was quantified on autoantigens comprising nucleic acids, proteins and lipids. Our results show that the relatively high complement consumption of nucleic acids is further increased upon binding of IgM and IgG. This is true even when serum complement levels are decreased due to complement consumption in SLE patients. A negative correlation between serum complement levels and ex vivo complement deposition on nucleic acid autoantigens is demonstrated. On the contrary, most protein and lipid autoantigens show positive correlation with C4 and C3 levels. Genetic analysis reveals that the non-synonymous variant rs1143679 in complement receptor type 3 is associated with an increased production of anti-dsDNA IgG antibodies. Notwithstanding, homozygous carriers of the previously reported susceptible allele (AA) have lower levels of dsDNA specific IgM among SLE patients. Regarding organ involvement we find that besides anti-C1q IgG, low levels of dsDNA specific IgM and low complement C4 binding to C1q are also associated with renal injury. In summary, nucleic acids maintain a skewed complement deposition balance when bound by IgG and IgM, depleting the early classical complement pathway from other physiological processes. Dysfunction of the receptor responsible for complement-mediated apoptotic debris removal promotes the development of autoantibodies targeting nucleic acids. These observations provide serological and genetic evidence for complement-mediated clearance deficiency of apoptotic debris in lupus.

Dataset Information

Autoantibodies Against Albumin in Patients With Systemic Lupus Erythematosus.

Publications

Autoantibodies Against Albumin in Patients With Systemic Lupus Erythematosus.

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