Clinical implications of the presence of anti-Ro(SSA) antibodies in patients with rheumatoid arthritis

doi:10.1016/0896-8411(88)90008-X

Journal of Autoimmunity

Volume 1, Issue 4, August 1988, Pages 381-388

https://doi.org/10.1016/0896-8411(88)90008-X Get rights and content

Abstract

The clinical and serologic findings in 25 patients with rheumatoid arthritis (RA) of more than 5 years' duration, who had antibodies to Ro(SSA) cellular antigen, were analyzed and compared with those in 50 anti-Ro(SSA) negative RA patients with similar disease duration. Ninety-six percent of the anti-Ro(SSA) positive patients were female, compared to 74% in the negative group. The majority of antibody positive patients had symmetric erosive synovitis, similar to that observed in the negative group. Extraarticular manifestations were similar in both groups, except for features of Sjögren's syndrome (keratoconjunctivitis sicca and positive labial salivary gland biopsy), which were significantly more common in patients with anti-Ro(SSA) antibodies. Anemia of chronic disease was also more common in these patients, as were rheumatoid factor (RF) and antinuclear antibodies (ANAs). No patient in either group had antibodies to ds-DNA or Sm and none developed clinical features suggestive of systemic lupus erythematosus (SLE). D-penicillamine, given in the majority of patients in both groups, produced adverse reactions in 72% of the anti-Ro(SSA) positive patients, but only in 27% of the negative ones. Thus, anti-Ro(SSA) antibodies seem to characterize a distinct group of RA patients who are almost exclusively female, express more activated B-cell function, have a high prevalence of Sjögren's features and commonly develop side effects to D-penicillamine.

References (26)

E.M. Tan
Autoantibodies to nuclear antigens (ANA): Their immunobiology and medicine
Adv. Immunol.
(1982)
J.R. Anderson et al.
Precipitating autoantibodies in Sjögren's disease
Lancet
(1961)
S.S. Kassan et al.
Antibody to a soluble acidic nuclear antigen in Sjögren's syndrome
Am. J. Med
(1977)
T.M. Tarpley et al.
Minor salivary gland involvement in Sjögren's syndrome
Oral Surg.
(1974)
C.A. Papasteriades et al.
HLA-alloantigen associations in Greek patients with Sjögren's syndrome
J. Autoimmunity
(1988)
M.A. Alspaugh et al.
Differentiation and characterization of autoantibodies and their antigens in Sjögren's syndrome
Arthritis Rheum.
(1976)
M.N. Manoussakis et al.
Serological profiels in subgroups of patients with Sjögren's syndrome
Scand. J. Rheumatol.
(1986)
J.S. Smolen et al.
HLA-DR antigens in systemic lupus erythematosus: association with specificity of autoantibody responses to nuclear antigens
Ann. Rheum. Dis.
(1987)
R.D. Sontheimer et al.
Serologic and HLA-associations in subacute cutaneous lupus erythematosus, a clinical subset of lupus erythematosus
Ann. Intern. Med.
(1982)
H.M. Moutsopoulos et al.
Correlative histologic and serologic findings of sicca syndrome in patients with systemic lupus erythematosus
Arthritis Rheum.
(1980)

W.L. Neston et al.

A serological marker for neonatal lupus erythematosus

Br. J. Dermatol.

(1982)

J.S. Scott et al.

Connective tissue disease, antibodies to ribonucleoprotein and congenital heart block

N. Engl. J. Med.

(1983)

H.M. Moutsopoulos et al.

Anti-Ro(SSA) positive rheumatoid arthritis (RA): a clinicoserological group of patients with high incidence of D-penicillamine side effects

Ann. Rheum. Dis.

(1985)

Cited by (30)

Allergic disorders and their risk factors in primary Sjögren's syndrome
2023, World Allergy Organization Journal
This study aimed to evaluate the prevalence of allergic disorders in patients with primary Sjögren's syndrome (pSS), compare it with that of patients with rheumatoid arthritis (RA), and examine the risk factors in patients with pSS.
We retrospectively examined the records of patients diagnosed with pSS and RA who regularly visited our department between 2010 and 2020. Allergic disorders included drug allergy, food allergy, allergic contact dermatitis (ACD), allergic rhinitis (AR)/allergic conjunctivitis (AC), and asthma.
Patients with pSS (292 patients) had a higher prevalence of food allergy, drug allergy, and AR/AC than those with RA (413 patients). The multivariate analysis revealed that patients with pSS who had drug allergy had a higher prevalence of food allergy, higher eosinophil levels, and higher positivity rates of anti–SS-related antigen A (SSA) antibodies than those without drug allergy; those with food allergy had a higher rate of ACD than those without food allergy and vice versa; those with AR/AC had a higher rate of ACD and asthma and higher eosinophil levels than those without AR/AC; those with asthma had a higher rate of AR/AC than those without asthma.
Patients with pSS had a higher prevalence of allergic disorders than those with RA. Among patients with pSS, the risk factors for drug allergy were food allergy, higher eosinophil levels, and positivity for anti-SSA antibodies, the risk factor for food allergy was ACD and vice versa, the risk factors for AR/AC were ACD, asthma, and high eosinophil levels, and the risk factor for asthma was AR/AC.
Scleroderma specific autoantibodies in rheumatoid arthritis and Sjögren's syndrome patients with interstitial lung disease: Prevalence and associations
2023, Journal of Translational Autoimmunity
Citation Excerpt :
This difference between the two groups was mainly attributed to statistically significant differences at strong rather than medium titers, with one fourth of RA ILD patients displaying SSc-specific antibodies at strong titers compared to only one patient among those with no evidence of lung involvement. Anti-Ro52 prevalence was similar between the two groups and accounted for 11.4% of the entire RA population, as previously shown [15,16]. While anti-Ro52 antibodies were previously linked with ILD in the context of IIM [17], such association was not observed in our study population.
Systemic sclerosis (SSc) has been classically linked to interstitial lung disease (ILD) development, often in association with specific SSc autoantibodies. In the present report, we aimed to estimate the prevalence of SSc autoantibodies in 60 seropositive RA and 41 primary SS patients complicated or not by ILD. SSc autoantibodies were determined in patients’ sera by a commercial immunoblot assay. RA ILD patients displayed higher frequency of SSc-specific antibodies at strong titers compared to RA-with no lung involvement (25% vs 3.1%, p = 0.01)[OR 95% CI:10.9 (1.2–94.5)], with no differences detected between primary SS groups. These data indicate that many seropositive RA ILD patients probably represent an overlap RA/SSc entity, requiring tailored diagnostic and therapeutic approach.
Autoantibodies to extractable nuclear antigens (ENAs) pattern in rheumatoid arthritis patients: Relevance and clinical implications
2021, Reumatologia Clinica
Citation Excerpt :
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by swelling, tenderness, progressive destruction of synovial lined joints, and progressive disability.1 RA is a disease with many faces, some of these correlate with the presence of certain autoantibodies for example anti Ro/SSA has an association with Sjögren's syndrome in RA.2–4 The presence of anti-Jo-1 in RA patients may indicate an overlap between RA and anti-synthetase syndrome (ASS) especially in anticitrullinated peptide/protein antibodies (ACPA) positive cases.5–11
To study the frequency of different autoantibodies to extractable nuclear antigens (ENAs) in rheumatoid arthritis (RA) patients and to correlate findings with clinical manifestations, disease activity and radiological damage.
A total of 230 RA patients were included and 75 healthy controls. In all patients rheumatological assessment was done and routine laboratory investigations and immune profile were performed in both patients and controls, including: RF, ACPA, ANA and anti-ENAs (Ro/SSA, La/SSB, U1-RNP, anti-Jo-1 and anti-Sm). Radiological damage was scored using Sharp/van der Heijde, and disease activity was evaluated by DAS28-ESR and DAS28-CRP.
RF was positive in 101 (43.9%), ACPA in 220 (95.7%), ANA in 58 (25.2%), anti Ro in 31 (13.5%), anti-La in 10 (4.3%), anti-Jo1 in 5 (2.2%) and anti-RNP in 2 (0.9%). Anti-Ro/SSA positively correlated with sicca symptoms (p = .02), RF titer (p < .001), ANA (p < .001), DAS28-ESR (p = .026), and DAS28-CRP (p = .003). Anti-La antibodies correlated positively with SJC (p = .001), TJC (p = .001), ANA (p < .001), DAS-28 ESR (p = .007). Anti-Jo-1 correlated positively with interstitial lung disease (ILD) (p ≤ .001), RF titer (p = .037) and ANA (p ≤ .001). Anti-RNP antibodies correlated positively with disease duration (p ≤ .001), ACPA titer (p ≤ .001) and ANA (p = .014). In the controls ANA was positive in two (2.7%), anti-Ro in three (4%), and none of the controls tested positive for other autoantibodies.
In RA patients, positive ANA is frequent and positively associated with anti-Ro, anti-La and anti-Jo1 autoantibodies. Screening for autoantibodies against other anti-ENAs seems mandatory in RA patients especially when ANA is positive. RA cases with positive Anti-Jo-1 may develop anti synthetase syndrome and ILD.
Estudiar la frecuencia de diferentes autoanticuerpos frente a antígenos nucleares extraíbles (ENA) en pacientes con artritis reumatoide (AR) y relacionar los hallazgos con las manifestaciones clínicas, la actividad de la enfermedad y el daño radiológico.
Se incluyeron un total de 230 pacientes con AR y 75 controles sanos. En todos los pacientes, la evaluación reumatológica, las investigaciones de laboratorio de rutina y el perfil inmune se realizaron tanto en pacientes como en controles, incluidos: RF, ACPA, ANA y anti-ENA (Ro/SSA, La/SSB, U1-RNP, anti-Jo-1 y anti-sm). El daño radiológico se puntuó con Sharp/van der Heijde y la actividad de la enfermedad se evaluó mediante DAS28-ESR y DAS28-CRP.
La RF fue positiva en 101 (43.9%), ACPA en 220 (95.7%), ANA en 58 (25.2%), anti Ro en 31 (13.5%), anti-La en 10 (4.3%), anti-Jo1 en 5 (2,2%) y anti-RNP en 2 (0,9%). Anti-Ro/SSA se correlacionó positivamente con los síntomas de sicca (p = .02), el título de RF (p < .001), ANA (p< .001), DAS28-ESR (p = .026) y DAS28-CRP (p = .003). Los anticuerpos anti-La se correlacionaron positivamente con SJC (p = .001), TJC (p = .001), ANA (p < .001), DAS-28 ESR (p = .007). El anti-Jo-1 se correlacionó positivamente con la enfermedad pulmonar intersticial (EPI) (p ≤ 0,001), título de RF (p = 0,037) y ANA (p ≤ 0,001). Los anticuerpos anti-RNP se correlacionaron positivamente con la duración de la enfermedad (p ≤ 0,001), el título de ACPA (p ≤ 0,001) y ANA (p = 0,014). En los controles, ANA fue positivo en dos (2.7%), anti-Ro en tres (4%) y ninguno de los controles dio positivo para otros autoanticuerpos.
En pacientes con AR, el ANA positivo es frecuente y se asocia positivamente con autoanticuerpos anti-Ro, anti-La y anti-Jo1. La detección de autoanticuerpos contra otros anti-ENA parece obligatoria en los pacientes con AR, especialmente cuando la ANA es positiva. Los casos de AR con Anti-Jo-1 positivo pueden desarrollar el síndrome de sintetasa e ILD.
Analysis of the cell populations composing the mononuclear cell infiltrates in the labial minor salivary glands from patients with rheumatoid arthritis and sicca syndrome
2016, Journal of Autoimmunity
Citation Excerpt :
Compared to RA patients without sicca symptomatology, the RA-sicca group manifested more frequent clinical and serological features that are commonly encountered in SS patients. These observations could suggest that sicca symptomatology could be attributed to a primary Sjögren’s syndrome coexisting with RA [28]. However, data from our LMSG biopsies revealed that the composition of the mononuclear cells infiltrates in RA-sicca patients differs significantly with that already described in pSS [7].
Sicca symptoms occur in around 30% of rheumatoid arthritis (RA) patients. Herein, we examined the characteristics of RA patients bearing sicca symptomatology (RA-sicca) with a special focus on the immunohistopathological features of their labial minor salivary gland (LMSG) biopsies.
Our cohort included 100 consecutive RA patients which were interrogated using a sicca symptoms questionnaire. Positive responders were evaluated for ocular and oral dryness and underwent an LMSG biopsy. All samples were immunohistochemically evaluated for the presence and distribution of specific leukocyte subsets using appropriate markers and for the expression of certain immunoregulatory molecules by salivary gland epithelial cells. Positively stained and total mononuclear cells (MNC) were counted in the entire section. Counts were expressed as cell frequency (percentage of cell type number/total infiltrating MNC number).
In the majority (86.1%) of the 44 RA-sicca cases, periductal infiltrates were observed in LMSG biopsies. The frequencies of infiltrating cell subtypes and their correlation with lesion severity were different from that previously described in primary Sjögren’s syndrome (pSS). Moreover, DCs and ΜΦs frequencies were increased in RA-sicca patients who had a biopsy focus score <1 and absence of anti-Ro/anti-La autoantibodies, in contrast to what was observed for B cells. In about half of the biopsies, salivary gland epithelial cells expressed CD80/B7.1 molecules, most commonly in patients with a positive biopsy or anti-Ro/anti-La autoantibodies.
LMSG infiltrates composition in RA-sicca patients is distinct from that described in pSS. These differences, further attest to diverse pathophysiologic processes operating in these two entities.
Detection of human-specific anti-La(SSB) antibodies in patients with rheumatoid arthritis
1995, Journal of Autoimmunity
Sera from anti-Ro(SSA) positive and negative patients with rheumatoid arthritis (RA) were compared with those from patients with primary Sjogren's syndrome (pSS) and systemic lupus erythematosus (SLE) with regard to anti-La(SSB) antibodies. Several assays for anti-La(SSB) (RNA precipitation, counterimmunoelectrophoresis, and immunoblotting) demonstrated the presence of such antibodies in selected anti-Ro(SSA) positive (10/19 in RA and 18/37 in pSS and SLE) but not in anti-Ro(SSA) negative sera. In agreement with previous reports, anti-La(SSB) antibodies from pSS and SLE patients uniformly reacted with various cellular extracts used as sources of La(SSB) antigen, including extracts from human cultured cells (HeLa), calf thymus and rabbit thymus. In contrast, while all 10 anti-La(SSB) sera from RA patients reacted with the human HeLa cell extracts, only three of them also reacted with calf and rabbit thymus extracts. These results were further supported by the analysis of a cohort of 70 consecutively selected sera (displaying monospecific anti-Ro(SSA) reactivity against calf thymus extract) from patients with various rheumatic disorders, where human-specific anti-La(SSB) were detected in two out of the five of RA patients studied.
Rheumatoid arthritis in south-east Europe
1992, Bailliere's Clinical Rheumatology
The clinical, serological and immunogenetic studies of RA in mediaterranean countries and other small tribal groups have added some more information that is valuable in understanding the pathogenesis of RA. However, the immunogenetic studies seem to be more helpful in understanding the mechanisms of initiation of disease and its dissimilarities in different ethnic groups than in discovering its cause. It should also be stressed that, in addition to genetic factors, other factors may influence disease expression. This proposal was supported by a study from Africa which revealed an increasing incidence and severity of RA in rural compared with urbanized African populations (Brighton, 1987). Thus, the variability factor influencing disease expression may lie in the environment (Woodrow, 1988).

View all citing articles on Scopus

View full text

Clinical implications of the presence of anti-Ro(SSA) antibodies in patients with rheumatoid arthritis

Abstract

Adv. Immunol.

Lancet

Am. J. Med

Oral Surg.

J. Autoimmunity

Differentiation and characterization of autoantibodies and their antigens in Sjögren's syndrome

Arthritis Rheum.

Serological profiels in subgroups of patients with Sjögren's syndrome

Scand. J. Rheumatol.

HLA-DR antigens in systemic lupus erythematosus: association with specificity of autoantibody responses to nuclear antigens

Ann. Rheum. Dis.

Serologic and HLA-associations in subacute cutaneous lupus erythematosus, a clinical subset of lupus erythematosus

Ann. Intern. Med.

Correlative histologic and serologic findings of sicca syndrome in patients with systemic lupus erythematosus

Arthritis Rheum.

A serological marker for neonatal lupus erythematosus

Br. J. Dermatol.

Connective tissue disease, antibodies to ribonucleoprotein and congenital heart block

N. Engl. J. Med.

Anti-Ro(SSA) positive rheumatoid arthritis (RA): a clinicoserological group of patients with high incidence of D-penicillamine side effects

Ann. Rheum. Dis.