The presence of masked antiribosomal P autoantibodies in healthy children

Anderson, Camille J.; Neas, Barbara R.; Pan, Zijian; Taylor-Albert, Elizabeth; Reichlin, Morris; Stafford, Haraldine A.

doi:10.1002/1529-0131(199801)41:1<33::aid-art5>3.3.co;2-x

Cited by 8 publications

(12 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…IgG anti-P antibody activity was detected in all treated samples, and none of the corresponding untreated sera (Table II). Based on our previous studies (15), these data suggest that anti-Ids to anti-P antibodies are present in SLE patients without overt anti-P antibodies. To prove this hypothe- Anti-P F(abЈ) 2 67 77 CF II F(abЈ) 2 3 0…”

Section: Characterization Of the Purified Igg Antibodies To Anti-p F(mentioning

confidence: 62%

“…Sera and plasma from healthy individuals have IgG antibodies to anti-P antibodies that inhibit antigen binding (12,15). To determine which portion of the anti-P antibody was reactive with these inhibitory antibodies, inhibition was tested against F(ab Ј ) 2 fragments of anti-P. As a source of inhibitor, plasma was used instead of serum, which reduces the potential contamination by intracellular ribosomal proteins during blood coagulation.…”

Section: Resultsmentioning

confidence: 99%

“…All patients fulfilled diagnostic criteria for SLE as defined by the American College of Rheumatology (14). Anti-P antibody positivity was determined by immunoblot and ELISA as described (15). Samples from multiple dates were available on most patients, and were repeatedly negative for anti-P antibodies in 10 patients.…”

Section: Methodsmentioning

confidence: 99%

“…Columns were exhaustively regenerated between individuals. Anti-P antibodies were also purified from the sera of 10 anti-P-negative SLE patients by affinity purification on nitrocellulose membranes coated with ribosomal P proteins as described (15). The presence of anti-P antibodies in the eluted material was confirmed with either the multiple antigenic peptide-"P-peptide"-specific ELISA (16), the ribosome-specific immunoblot, or both (12).…”

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Anti-idiotypic antibodies prevent the serologic detection of antiribosomal P autoantibodies in healthy adults.

Pan

Anderson²,

Stafford³

1998

J. Clin. Invest.

View full text Add to dashboard Cite

A subset of SLE patients has serologically detectable autoantibodies to the ribosomal P proteins (anti-P). We reported the discovery of covert anti-P antibodies and their masking IgG-inhibitory antibodies in the sera of healthy adults. The aim of this study was to determine if these IgGinhibitory antibodies are anti-idiotypic antibodies (anti-Ids). IgG and IgG-depleted fractions of plasma from two healthy adults were assayed for inhibition of anti-P F(ab Ј ) 2 binding to the ribosomal P proteins in immunoblot. Anti-P antibody activity was completely inhibited by plasma IgG, whereas there was no inhibition by IgG-depleted plasma. IgG-inhibitory antibodies recognized a cross-reactive epitope among anti-P from different SLE patients. Plasma IgG from one healthy adult was depleted of pepsin agglutinators and generic anti-F(ab Ј ) 2 antibodies by adsorption with an affinity column prepared with normal IgG F(ab Ј ) 2 . Unretained IgG bound exclusively to anti-P F(ab Ј ) 2 in ELISA. Using four affinity columns, we isolated IgG anti-Ids to anti-P antibodies from four healthy adults. These purified anti-Ids bound to anti-P F(ab Ј ) 2 from a healthy adult and SLE patients. They did not bind to F(ab Ј ) 2 fragments prepared from normal IgG or anti-dsDNA. Ribosomal antigens blocked this antiId-Id interaction. Purified anti-Ids inhibited the binding of anti-P F(ab Ј ) 2 from patients to ribosomal P proteins. SLE patients without overt anti-P antibodies also possessed IgG anti-Ids to anti-P antibodies. We conclude that IgG-inhibitory antibodies are anti-Ids to anti-P antibodies, and are directed to public idiotopes on anti-P antibodies. These anti-Ids may be part of an Id network that regulates anti-P antibody expression, and perhaps pathogenicity. ( J. Clin. Invest. 1998. 102:215-222.)

show abstract

Section: Characterization Of the Purified Igg Antibodies To Anti-p F(mentioning

confidence: 62%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Anti-idiotypic antibodies prevent the serologic detection of antiribosomal P autoantibodies in healthy adults.

Pan

Anderson²,

Stafford³

1998

J. Clin. Invest.

View full text Add to dashboard Cite

show abstract

“…Autoantibodies to ribosomal P proteins (anti-P) are regarded as specific for patients with systemic lupus erythematosus. Stafford and colleagues (21)(22)(23) demonstrated that in healthy individuals who tested negative for anti-P antibodies by conventional serologic screenings anti-P antibodies were in fact readily detectable after removal of the inhibitory antibodies. Similarly, autoantibodies to the E2 subunit of the pyruvate dehydrogenase complex, thought to be specific to patients with primary biliary cirrhosis, are present but inhibited by anti-Ids in healthy individuals (24).…”

Section: Discussionmentioning

confidence: 99%

The lack of anti-idiotypic antibodies, not the presence of the corresponding autoantibodies to glutamate decarboxylase, defines type 1 diabetes

Oak

Gilliam

Landin‐Olsson

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Autoantibodies to glutamate decarboxylase 65 (GAD65Ab) are commonly believed to be a major characteristic for type 1 diabetes (T1D). We investigated the presence of GAD65Ab in healthy individuals (n ‫؍‬ 238) and first-degree relatives (FDRs) of T1D patients (n ‫؍‬ 27) who tested negative for GAD65Ab in conventional RIAs. Sera were applied to affinity columns coated with GAD65-specific mAbs to absorb anti-idiotypic antibodies (anti-Ids). The absorbed sera were analyzed for binding to GAD65 by RIAs. Both healthy individuals and FDRs present GAD65Ab that are inhibited by anti-Id, masking them in conventional detection methods. The presence of GAD65Ab-specific anti-Ids was confirmed by competitive ELISA. Remarkably, T1D patients (n ‫؍‬ 54) and Stiff Person Syndrome patients (n ‫؍‬ 8) show a specific lack of anti-Ids to disease-associated GAD65Ab epitopes. Purified anti-Ids from healthy individuals and FDRs inhibited the binding of GAD65Ab from T1D patients to GAD65. We conclude that masked GAD65Ab are present in the healthy population and that a lack of particular anti-Ids, rather than GAD65Ab per se, is a characteristic of T1D. The lack of these inhibitory antibodies may contribute to T cell activation by GAD65Ab.T ype 1 diabetes (T1D) is an autoimmune disease characterized by the presence of serologically detectable autoantibodies to multiple islet cell autoantigens. Autoantibodies to glutamate decarboxylase 65 (GAD65Ab) can be detected in the majority of new-onset T1D patients (1), in patients with latent autoimmune diabetes in adults (for review see ref.2), diabetes-related polyendocrine diseases (for review see ref.3), and in some rare neurologic diseases, notably Stiff Person Syndrome (SPS) (4), but rarely in the general population. GAD65Ab often herald the onset of T1D by months or years and are used to predict disease together with other islet cell autoantibodies (5, 6). The function of these autoantibodies and their B cells in the pathogenesis of T1D is not clear, especially as a patient with severe B cell deficiency and diabetes was reported (7). Although GAD65Ab are often considered to be an epiphenomenon resulting from the autoimmune destruction of the pancreatic ␤ cells, some studies suggest that they may be involved in antigen processing and presentation and thus modulate the immune response (8-10). This hypothesis is supported by a recent study demonstrating a pathogenic role of autoantibodies by enhancing islet cell antigen presentation to autoreactive T cells (11). Harbers et al. (11) showed that both antigen-specific CD8 ϩ T cells and antigenspecific antibodies were necessary for the development of autoimmune diabetes in transgenic mice that express a membranebound form of ovalbumin in pancreatic ␤ cells.To investigate the possible role of GAD65Ab in T1D pathogenesis, we previously injected young nonobese diabetic (NOD) mice with the GAD65-specific mAb b96.11 (12). This antibody specificity was shown earlier to be predictive of the development of T1D in humans (13). We found that this treatment i...

show abstract

Prevalence of autoantibodies to ribosomal P proteins in juvenile-onset systemic lupus erythematosus compared with the adult disease

Reichlin

Broyles

Hübscher

et al. 1999

Arthritis & Rheumatism

Self Cite

View full text Add to dashboard Cite

Objective. To determine the prevalence of anti-ribosomal P (anti-P) proteins in several groups of patients with juvenile-onset systemic lupus erythemato-sus (SLE) in comparison with the prevalence in adult SLE. Methods. Serum samples were pooled together from 3 cohorts of patients with juvenile-onset SLE in 3 different medical centers and from a miscellaneous group of juvenile-onset SLE patients whose samples were sent by regional physicians. Sera were studied for the presence of anti-P using 2 assays: Western blot with ribosomes as antigen, and an enzyme-linked immu-nosorbent assay with the COOH-terminal 22 amino acids of the ribosomal P protein in a multiantigenic peptide format as antigen. Sera found positive by both tests were considered positive for anti-P antibodies. Findings from similar studies involving a large cohort of patients with adult-onset SLE from Oklahoma City were used for comparison. Results. The prevalence of anti-P antibodies in the pooled sample of juvenile-onset SLE sera was 45 of 108, or 42%, while in the adult cohort from Oklahoma City, 20 of 260, or 7.7%, were positive for anti-P (odds ratio [OR] 9.6, P < 10 8 by Fisher's exact test). In addition, it was shown that 12 of 13 patients with both anti-P and anti-double-stranded DNA (anti-dsDNA) in the juvenile SLE cohort had nephritis, while only 8 of 22 patients without both antibodies were nephritic (OR 21.0, P < 10 8). It was also shown that in 9 illustrative cases, the levels of anti-P and anti-dsDNA antibodies usually varied together and in concordance with the clinical activity as measured by the SLE Disease Activity Index (SLEDAI). Finally, anti-P-positive and anti-P-negative patients had a similar prevalence of anti-dsDNA, anti-Ro/SSA, and anti-La/SSB antibodies, but patients with anti-P had a higher prevalence of anti-U1 RNP and anti-Sm (P 0.041 and P 0.0385, respectively , by Fisher's exact test). Conclusion. Antibodies to ribosomal P protein are more prevalent in juvenile-onset SLE than in adult-onset SLE. Levels of antibodies to ribosomal P protein vary with the clinical disease activity as measured by the SLEDAI, often in concordance with the levels of anti-dsDNA. The presence of both anti-P and anti-dsDNA antibodies was powerfully associated with nephritis in the cohort of patients for whom comprehensive clinical and serologic data were available.

show abstract

The presence of masked antiribosomal P autoantibodies in healthy children

Cited by 8 publications

References 0 publications

Anti-idiotypic antibodies prevent the serologic detection of antiribosomal P autoantibodies in healthy adults.

Anti-idiotypic antibodies prevent the serologic detection of antiribosomal P autoantibodies in healthy adults.

The lack of anti-idiotypic antibodies, not the presence of the corresponding autoantibodies to glutamate decarboxylase, defines type 1 diabetes

Prevalence of autoantibodies to ribosomal P proteins in juvenile-onset systemic lupus erythematosus compared with the adult disease

Contact Info

Product

Resources

About