Titers of Antibodies to Rana in Rheumatoid Arthritis and Normal Sera

Venables, P. J. W.; Roffe, Lindsay; Erhardt, C. C.; Maini, R. N.; Edwards, J M; Porter, Allison

doi:10.1002/art.1780241201

Cited by 51 publications

(16 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One explanation of the observations is the possibility that RANA may show immunological identity to a (non-EBV) nuclear antigen, and we have found some support for this idea in our studies [25]. Thus in RA an autoimmune response to the nuclear antigen (indistinguishable serologically) may summate with an anti-RANA response.…”

Section: Hla Class II Antigens: Susceptibility Factors Initiators Asupporting

confidence: 65%

“…The paradox is that IgG anti-RANA antibodies contrast with similar or marginally elevated levels of antibodies to EBNA-1 or to EBV-viral capsid antigens in RA [25,29,30]. This pattern is not consistent with a persistent EBV infection of the type proposed on the basis of substantially increased levels to all EBV-viral antigens in nasopharyngeal carcinoma [31].…”

Section: Hla Class II Antigens: Susceptibility Factors Initiators Amentioning

confidence: 87%

“…Molecular mimicry between HLA-DR and the Epstein-Barr virus (EBV) may be of aetiological importance. For some years we have been impressed by the remarkably elevated levels of IgG antibodies to rheumatoid arthritis nuclear antigen (RANA) in patients with RA and have speculated on the significance of this finding [25,26]. This was originally interpreted as possibly indicating a link between EBV infection and RA [27], but since we documented a handful of patients with classical RA who had no serological evidence of previous EBV infection, this agent could not be the sole cause of RA.…”

Section: Hla Class II Antigens: Susceptibility Factors Initiators Amentioning

confidence: 96%

See 2 more Smart Citations

Heberden Oration, 1988 Exploring Immune Pathway's in Rheumatoid Arthritis

Maini

1989

Rheumatology

View full text Add to dashboard Cite

Section: Hla Class II Antigens: Susceptibility Factors Initiators Asupporting

confidence: 65%

Section: Hla Class II Antigens: Susceptibility Factors Initiators Amentioning

confidence: 87%

Section: Hla Class II Antigens: Susceptibility Factors Initiators Amentioning

confidence: 96%

See 1 more Smart Citation

Heberden Oration, 1988 Exploring Immune Pathway's in Rheumatoid Arthritis

Maini

1989

Rheumatology

View full text Add to dashboard Cite

“…RANA was shown to be a nuclear antigen expressed exclusively in Epstein-Barr virus (EBV) genome-positive B-lymphoblast lines (3). With more sensitive assays, anti-RANA can now be detected in many normal sera, although in lower titer than in RA sera (4)(5)(6)(7), and also during recovery from acute infectious mononucleosis (IM) (5).…”

mentioning

confidence: 99%

Antibodies to the Epstein-Barr virus nuclear antigen and to rheumatoid arthritis nuclear antigen identify the same polypeptide.

Billings¹,

Hoch²,

White³

et al. 1983

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

View full text Add to dashboard Cite

Patients with seropositive rheumatoid arthritis (RA) have elevated titers of precipitating antibody toward an antigen designated RA nuclear antigen (RANA). Anti-RANA reactivity has been associated with prior Epstein-Barr virus (EBV) be reactive when a complement fixation assay was used in the immunoblot. Finally, when the Mr 80,000 antigen was used to absorb an anti-RANA/anti-EBNA serum, both antibodies were reduced.The rheumatoid arthritis nuclear antigen (RANA) was first identified in WI-L2 cells by a precipitating antibody seen in the sera of most rheumatoid arthritis (RA) patients but uncommonly in normal sera (1, 2). RANA was shown to be a nuclear antigen expressed exclusively in Epstein-Barr virus (EBV) genome-positive B-lymphoblast lines (3). With more sensitive assays, anti-RANA can now be detected in many normal sera, although in lower titer than in RA sera (4-7), and also during recovery from acute infectious mononucleosis (IM) (5).The relation between RANA and the Epstein-Barr nuclear antigen (EBNA) (8) has remained a matter of some uncertainty. RANA was originally detected in extracts of EBV-infected cells by precipitation reactions but has also been detected in an assay using heat fixation and anti-IgG immunofluorescence (IF) (1, 2). EBNA was originally assayed on acetone-fixed cells by anticomplement immunofluorescence (ACIF) and later by complement fixation with soluble cell extracts (8, 9). EBNA staining typically displays a plaque-like or diffuse stain confined to the nucleus (8), whereas RANA is more granular or speckled and sometimes extends into the cytoplasm (2). RANA and EBNA staining patterns are maximally expressed at different times in the cell cycle of WI-L2 cells and they are differentially expressed in somatic cell hybrids (10, 11). Significant differences in anti-EBNA and anti-RANA titers have been reported for individual sera-notably, those from Burkitt lymphoma patients (3). However, antibodies reactive with EBNA and RANA have been shown to arise roughly in parallel after EBV infection (5), and anti-EBNA'and anti-RANA titers in individual RA patients and normal adults are closely correlated (4, 6). Only EBNA has been partially purified and characterized; however, the EBNA sizes reported range from Mr 48,000 to Mr 100,000 (12-15 Nuclear Isolation and Extraction. After washing in phosphate-buffered saline (150 mM NaCl/10 mM sodium phosphate, pH 7.4) containing 0.2 mM phenylmethylsulfonyl fluoride, cells were swollen for 5 min in reticulocyte standard buffer (RSB; 10 mM NaCl/10 mM Tris-HCl, pH 7.4/1.5 mM MgCl2/ 0.2 mM phenylmethylsulfonyl fluoride). The cells were pelleted and homogenized in RSB containing 0.2% Nonidet P-40; then nuclei were sonicated in 3-5 vol of the same buffer adjusted to 0.2-0.35 M NaCl. After 30 min on ice, the nuclear extract was centrifuged at 10,000 x g and used as a source of antigen. When heat fractionation was used, the extract was diluted to ca. 0.15 M NaCl and rapidly heated to 750C, held for 10 min, chilled, and centrifuged at 20,000 X g for 1...

show abstract

“…In addition, patients with RA have numerous abnormal cellular and humoral immune responses to EBV. Among these, the antibodies that react with EBV-induced nuclear antigens (RANAs) were of particular interest, because they were almost uniquely associated with RA [10]. Moreover, there are nucleotide sequences that are specific for the EBV-associated nuclear antigen-I (EBNA-I), which are shared with some sequences in the human genome [11].…”

Section: Introductionmentioning

confidence: 99%

Non-HIV retroviral associations with rheumatic disease

Zucker‐Franklin

2000

Curr Rheumatol Rep

View full text Add to dashboard Cite

While the human T-cell lymphotropic virus type I (HTLV-I) is the recognized cause of adult T cell leukemia, it is also associated with non-neoplastic, ostensibly autoimmune conditions, such as tropical spastic paraparesis. Moreover,among carriers of HTLV-I, the virus is strongly implicated in the development of a type of arthritis, which resembles rheumatoid arthritis (RA). Mice transgenic for HTLV-I tax develop RA-like pathology and Sjögren's syndrome. Patients with RA and SS in HTLV-I nonendemic regions, such as the United States, are usually serologically negative for antibodies to the structural proteins of HTLV. However, they appear to harbor HTLV-I tax in their peripheral blood mononuclear cells three times as often as individuals who present as healthy blood donors. Because HTLV-I tax transactivates numerous inflammatory cytokines and is not normally found in the human genome, treatment with tax antisense oligonucleotides may provide a new therapeutic approach for selected RA patients proven to be HTLV-I "tax only" positive.

show abstract

Titers of Antibodies to Rana in Rheumatoid Arthritis and Normal Sera

Cited by 51 publications

References 13 publications

Heberden Oration, 1988 Exploring Immune Pathway's in Rheumatoid Arthritis

Heberden Oration, 1988 Exploring Immune Pathway's in Rheumatoid Arthritis

Antibodies to the Epstein-Barr virus nuclear antigen and to rheumatoid arthritis nuclear antigen identify the same polypeptide.

Non-HIV retroviral associations with rheumatic disease

Contact Info

Product

Resources

About