Ana-Negative Lupus Presenting with Heart Failure and Severe Valvular Dysfunction: Case Report and Review of the Literature

Antinuclear antibody (ANA) negative lupus is an important subset of the systemic lupus erythematosus (SLE) disease spectrum. Since the introduction of human cell line for ANA assay, the occurrence of true ANA-negative SLE has been a rare clinical phenomenon. The nature of cardiac involvement in ANA-negative SLE is not well understood, although any cardiac involvement, including valvular dysfunction, should be considered as a presenting manifestation of SLE irrespective of serology status. Early recognition and intervention appears to be associated with decreased morbidity.The following report describes our first case of ANA-negative SLE with an initial presentation of severe cardiac valvular dysfunction and heart failure. It also characterizes the spectrum of disease severity in ANA-negative SLE and demonstrates how aggressive SLE therapy can improve cardiac disease.     

Two cases of antinuclear antibody negative lupus showing increased proportion of B cells lacking RP105

B cells lacking RP105 molecule, a member of the Toll-like receptor family, were increased in the peripheral blood of 2 patients with antinuclear antibody (ANA) negative systemic lupus erythematosus (SLE). The increased proportion of RP105-lacking B cells was associated with disease activity in patients with ANA-negative SLE. When there are no significant serological markers for SLE, analysis of expression of RP105 may be helpful in evaluation of activity in ANA-negative SLE. We describe a new approach, using phenotyping of B cells, to evaluate activity of ANA-negative SLE.     

Antinuclear antibody-negative systemic lupus erythematosus in a case with pregnancy

We described a 30-year-old pregnant woman developing antinuclear antibodies (ANA)-negative systemic lupus erythematosus (SLE) accompanied with arthritis, malar rash, lymphopenia, autoimmune hemolytic anemia, pericardial and pleural effusion, proteinuria and seizures. All serum autoantibodies except anti-Ro antibody were negative. An artificially induced abortion was performed to prevent SLE deterioration. Steroid and cyclophosphamide therapy were effective for this patient. During the 2-year follow-up period, her ANA and other SLE-related autoantibodies in serum remained negative. This case suggests that ANA may not be required in the pathogenesis of SLE, even in the case with pregnancy, and ANA-negative SLE may also have a dangerous clinical course.     

DNA skin tests in patients with definite or suspected systemic lupus erythematosus and in dermatological control patients. A long-term follow-up study

This study presents a long-term clinical and immunological follow-up of 62 patients during 1971 and 1973, tested intradermally with DNA derived from calf thymus. The DNA skin test is positive in almost all clear-cut cases of SLE. In addition, the DNA skin test was positive in 16 patients, but the criteria for SLE were not met at the time of testing. During the follow-up, 7 out of these 16 patients developed definite SLE, 2 developed subacute cutaneous LE and 3 developed ANA-negative SLE. This suggests that a positive DNA skin test may precede the development of SLE or some of its subtypes. All our SLE patients with skin test reactivity presented cutaneous disease manifestations suggesting that similar pathogenetic mechanisms may be involved in DNA tests and natural SLE skin lesions. Because the positive DNA skin test showed correlation with ANA, anti-DNA antibodies, cryoglobulins, lupus anticoagulant and depressed C3 and C4 values, humoral factors may be partly responsible. However, DNA skin test reactivity was also positive in ANA-negative SLE, suggesting that other mechanisms may also be involved.     

Antiphospholipid antibodies in a series of 25 cases of lupus without antinuclear antibodies. Comparison with a series of 91 lupus patients with antinuclear antibodies

Twenty-five patients with at least 3 of 1982 ARA criteria of SLE but without the ANA, were compared with 91 patients with 4 or more of the ARA criteria of lupus with positive ANA. The ANA-negative group was characterised by the low incidence of skin involvement, serous effusions and alopecia, and a relatively high incidence of thrombocytopaenia and venous and arterial thrombosis. Three types of antiphospholipid antibodies were looked for: the VDRL, antiprothrombinase and anticardiolipin antibodies by an immuno-enzymatic method. The VDRL was the only antibody which was significantly commoner in the ANA-negative group. Statistical studies showed that the three methods of demonstrating antiphospholipid antibodies detected crossed but not identical specificities. In the ANA-positive group only the antiprothrombinase was associated with a high incidence of venous thrombosis and stroke. In the ANA-negative group, only the anticardiolipin antibodies were associated with a high incidence of arterial or venous thrombosis. Two subgroups may be identified in the group of ANA-negative lupus patients: firstly, those with high anticardiolipin antibody titres with a high incidence of thrombotic and haematological complications, and, secondly, patients with low anticardiolipin antibody levels with a high incidence of cutaneous involvement, serous effusions and Raynaud's phenomenon.     

The prevalence and significance of positive antinuclear antibodies in patients with fibromyalgia syndrome: 2-4 years' follow-up

The aim of this study was to ascertain whether fibromyalgia patients with positive ANA develop other features of connective tissue disease over 2-4 years' follow-up. Patients attending our clinic with a diagnosis of fibromyalgia were identified. All ANA-positive patients (n = 12) were recruited and matched for age and sex with 12 ANA-negative FMS patients. As further control groups, patients with a diagnosis of osteoarthritis (OA) were included. A screening questionnaire for possible features of connective tissue disease was sent to all participants. Patients who had three or more positive criteria were invited for further assessment. The ANA-positive rate was 12/137 (8.8%) in FMS and 20/225 (8.9%) in OA patients. All ANA positivity was at a low titre. Fourteen out of 20 (70%) FMS patients and 17/30 (56.7%) OA patients had three or more criteria (P = 0.34). No significant differences in the number of the positive criteria were found between those who were ANA positive or negative in both groups. On full assessment we found one patient who fulfilled the criteria for SLE from the ANA-positive FMS group and one in the ANA-negative group who fulfilled the criteria for primary Sj?gren's syndrome. Of the patients with OA, one who was ANA positive was diagnosed as having rheumatoid arthritis. The results from our study show that ANA (at least in low titre) is not a good predictor of the future development of connective tissue.     

First Evaluation Study of the Dutch Working Party on Silicone Breast Implants (SBI) and the Silicone-Related Symptom Complex (SRSC)

This cohort study evaluates the postoperative prevalence of antinuclear antibodies (ANA) in relation to symptoms related to the so-called silicone-related symptom complex (SRSC). A total of 63 women who underwent mastectomy followed by immediate breast reconstruction with a silicone implant (SBI) between Septembber 1990 and May 1995 at the University Hospital Rotterdam/Daniel den Hoed Cancer Center, participated voluntarily in the study. Their sera were tested for the presence of antinuclear antibodies (ANA) and at the same time they were screened for the prevalence of SRSC-related symptoms by questionnaire. All patients were also examined physically. Sixteen per cent of the women were ANA positive. There was no difference in SRSC expression between ANA-positive and ANA-negative women. The lack of difference in symptom expression between the ANA-positive and ANA-negative women and the rather low complaint percentage proves that if ANA positivity is related to the SRSC, we found no evidence that patients with a SBI with a positive ANA differed from the ANA-negative patients. Received: 23 November 1999 / Accepted: 22 March 2000     

Clinical features of antinuclear antibodies-negative type 1 autoimmune hepatitis

Aim:  Antinuclear antibodies (ANA) are the main serologic markers of type 1 autoimmune hepatitis (AIH); however 20–30% of patients are negative for ANA. We assessed the clinical features of ANA-negative patients.
Methods:  A retrospective analysis was performed of 176 patients with type 1 AIH (153 females, median age 55 years). A diagnosis of AIH was made based on the revised scoring system proposed by the International Autoimmune Hepatitis Group. ANA titers were measured using a standard indirect immunofluorescence technique.
Results:  Thirty-eight patients (22%) had low titers of ANA (1:40 or 1:80), and 114 (65%) had high titers (≥ 1:160). Of 24 ANA-negative patients, 15 were positive for smooth muscle antibodies (SMA). Three of nine both ANA- and SMA-negative patients developed ANA during follow-up. The other six were diagnosed based on histological characteristics. Thirteen ANA-negative patients relapsed after the normalization of serum alanine aminotransferase (ALT) levels. ANA-negative patients more frequently showed acute presentation and, at presentation, had lower serum immunoglobulin G levels, higher serum levels of bilirubin and transaminase, and higher frequencies of histological acute hepatitis and zone 3 necrosis than those with high titers. However, the frequency of advanced stage of fibrosis was similar. The response to corticosteroids was not different among the three groups.
Conclusions:  ANA-negative type 1 AIH shows acute-onset more frequently but may include not only acute autoimmune hepatitis, but also acute exacerbation of inactive chronic disease. Regarding the diagnosis of ANA-negative AIH, the determination of ANA during follow-up and the response to immunosuppressive treatment may be helpful.     

Clinicopathological significance of antinuclear antibodies in non-alcoholic steatohepatitis

Aim: Serum antinuclear antibodies (ANA) are occasionally noted in patients with non-alcoholic steatohepatitis (NASH). We examined the significance of ANA in NASH. Methods: We compared clinicopathological features in patients with ANA-positive NASH (n = 35) and ANA-negative NASH (n = 36). Inflammatory cell profiles and the distribution of oxidative stress markers were also examined immunohistochemically. Results: ANA-positive NASH was significantly associated with female gender (P = 0.005), high degree of portal inflammation (P = 0.039), interface activity (P = 0.036) and hepatocellular ballooning (P = 0.0008). In addition, ANA of high titer (320-fold or more) was significantly associated with the histological grade and stage of NASH (P = 0.02). The degree of steatosis wais rather mild in the high-titer ANA group(P = 0.01). The analysis of inflammatory cell profiles revealed that CD3-positive T cells were predominant and plasma cells were rather few in the portal area and hepatic lobules in both ANA-positive and ANA-negative groups. There was no difference in the distribution of oxidative stress markers between ANA-positive and ANA-negative groups. Conclusion: These findings suggest that the presence of ANA may be related to the progression of NASH and that a different type of autoimmune mechanism may be involved in the pathogenesis of NASH with ANA, compared to the pathogenesis of autoimmune hepatitis.     

Recently characterised autoantibodies and their clinical significance

Multisystem autoimmune diseases such as systemic lupus uythcmatosus (SLE), primary Sjögrcn's syndrome (SS), sclcroderma and polymositis are characterised by the presence of antinuclear antibodies (ANAs). Immunoblotting and cDNA cloning studies reveal that the autoantigens of the multisystem autoimmune dixsucs are important proteins involved in nucleic acid metabolism, including tRNA charging, intron splicing, DNA uncoiling, and RNA polymuase co-factors.
Each spaific syndrome associates with a restricted variety of ANAs e.g. anti-La with primary SS, anti-Sm with SLE, and-synthetase enzymes with myositis, and-topoisomerase 1 (Scl 70) with scleroderma, and anti-centromere with CREST. Precise characterisation of an ANA provides valuable diagnostic and prognostic information, and should be performed when an ANA is detected.     

Antinuclear antibody-positive cohort constitutes homogeneous entity in juvenile idiopathic arthritis

Objective. To identify a homogeneous entity for antinuclear antibody (ANA)-positive patients suffering from juvenile idiopathic arthritis (JIA).

Methods. All of the clinical features were recorded retrospectively. ANA positivity was defined as more than twice positive results at a titer of > 1:100. The correlation between ANA positivity and clinical parameters was assessed by multiple logistic regression analysis.

Result. Of 120 patients, 49 patients were ANA positive (31 oligoarthritis, 18 rheumatoid factor [RF]-negative polyarthritis) and 71 patients were ANA negative (48 oligoarthritis, 23 RF-negative polyarthritis), and were recruited retrospectively to this study according to the International League of Associations for Rheumatology (ILAR) criteria. In ANA-positive cohort, the characteristics of early-onset age, female predominance, and asymmetric arthritis were observed compared with ANA-negative cohort including oligoarthritis and RF-negative polyarthritis. Correspondingly, we found that ANA-positive cohort had higher cumulative number of joints affected at 9 and 12 months after disease presentation than ANA-negative cohort, had lower frequency of occurrence of image change, and had a different pattern of affected arthritis than ANA-negative cohort, which was more likely to have knee involvement and less likely to have hip and shoulder involvement. ANA positivity correlated strongly with asymmetric arthritis, female predominance and wrist involvement.

Conclusion. This study demonstrates that ANA-positive cohort divided into different subgroups by present ILAR criteria share the similar features and suggests that ANA positivity might serve as a novel potential value for JIA classification.     

Expression and clinical significance of antinuclear antibody in hepatitis C virus infection

BACKGROUND: The prevalence of antinuclear antibody (ANA) has been documented in patients with hepatitis C virus (HCV) infection. We attempted to determine the titer and to characterize the patterns and clinical significance of ANA in HCV infection. STUDY: Forty-eight consecutive patients with positive anti-HCV antibody and positive HCV RNA were included in this study. Sera from patients were tested for ANA and anti-smooth muscle antibody by indirect immunofluorescence. Serum aminotransferase, alkaline phosphatase, alpha-fetoprotein, and cryoglobulin levels also were determined. RESULTS: Eleven (23%) of 48 HCV-infected patients were positive for ANA. Antinuclear antibody revealed speckled pattern in 10 (91%) of the 11 ANA-positive HCV-infected patients. Twenty (54%) of 37 ANA-negative HCV-infected patients had detectable pattern with equivocal titer (titer <1.5). The ANA pattern was speckled in all 20 patients. Hepatitis C virus-infected patients with positive ANA were older than the HCV-infected patients with negative ANA (62.90 +/- 11.05 years vs. 56.46 +/- 14.94 years, respectively; p < 0.1). Serum levels of aspartate aminotransferase (39.36 +/- 14.98 IU/L vs. 30.70 +/- 23.15 IU/L, p < 0.05), alkaline phosphatase (189.00 +/- 75.63 IU/L vs. 122.41 +/- 40.88 IU/L, p < 0.01), and alpha-fetoprotein (47.72 +/- 80.47 pg/dL vs. 7.00 +/- 8.28 pg/dL, p < 0.01) were higher in ANA-positive HCV-infected patients than in ANA-negative HCV-infected patients, respectively. There were no significant differences in gender, alanine aminotransferase, anti-smooth muscle antibody, or cryoglobulin between the two groups. CONCLUSIONS: Antinuclear antibody was present in 11 (23%) of 48 patients with HCV infection in our study. Speckled pattern is the major expression pattern of ANA in HCV infection. Antinuclear antibody-positive HCV-infected patients have significantly higher serum aspartate aminotransferase, alkaline phosphatase, and alpha-fetoprotein levels than ANA-negative HCV-infected patients.     

Autoimmune uveitis in children: clinical correlation between antinuclear antibody positivity and ocular recurrences

OBJECTIVE: The aim of this study was to identify the correlation between antinuclear antibody (ANA) titre and the onset and clinical course of uveitis in children with juvenile idiopathic arthritis (JIA) or without any other systemic autoimmune disease, i.e., idiopathic uveitis (IU). METHODS: Twenty-two patients affected by uveitis were examined. Ten had JIA-associated uveitis, 12 had IU. Follow-up ranged from 7 to 101 months. The ANA were titrated three times per year and additionally in case of ocular recurrences. All patients were treated with immunosuppressive drug combination therapy (IDCT). RESULTS: JIA-associated uveitis: ocular recurrences were noted in three ANA-positive patients and in one ANA-negative patient. IU uveitis: ocular recurrences were noted in one ANA-positive and in one ANA-negative patient. No significant rise in ANA titre was noted in either group during uveitis recurrence. CONCLUSIONS: (1) ANA had no value in predicting the recurrence of uveitis. (2) IDCT does not influence ANA production.     

Antinuclear antibody-negative systemic sclerosis

ObjectiveTo examine the demographic and clinical characteristics of systemic sclerosis (SSc) patients without antinuclear antibodies (ANA) compared to ANA-positive patients.MethodsSSc patients enrolled in the Scleroderma Family Registry and DNA Repository were included. Relevant demographic and clinical data were entered by participating sites or obtained by chart review. ANA and SSc-related antibodies were determined in all investigated patients using commercially available kits at our laboratories.ResultsThis study included 3249 patients, of whom 208 (6.4%) were ANA negative. The proportion of male patients was higher in the ANA-negative group (OR = 1.65; p = 0.008). ANA-negative patients experienced less vasculopathic manifestations of SSc. The percent predicted diffusing capacity of carbon monoxide (DLCO) was higher in ANA-negative patients (p = 0.03). Pulmonary arterial hypertension (PAH) per right heart catheterization was less common in the ANA-negative group (OR = 0.28; p = 0.03). Furthermore, patients with negative ANA had a lower prevalence of telangiectasias and digital ulcers/pits (OR = 0.59, p = 0.03 and OR = 0.38, p = 0.01, respectively). Although diffuse cutaneous involvement was more common, the modified Rodnan Skin Score (mRSS) was lower in the ANA-negative group (2.4 points lower, p = 0.05). Furthermore, they experienced more malabsorption (p = 0.05). There was no difference in the frequency of pulmonary fibrosis or scleroderma renal crisis. All-cause mortality was not different between the 2 groups (p = 0.28).ConclusionsIn conclusion, the results of this study suggest that SSc patients who are ANA negative constitute a distinct subset of SSc with less vasculopathy (less PAH, digital ulcers, and fewer telangiectasias), a greater proportion of males, and possibly, more frequent lower gastrointestinal involvement.     

Antinuclear antibodies (ANA): Immunologic and clinical significance

The methods currently used for the detection of ANA have been analyzed, with emphasis on their practical application to the diagnosis of the CTD. The use of the indirect IF-ANA test was recommended as a screening procedure to detect ANA. The need to standardize the technique using a single substrate and fluorescent conjugates with uniform $\text{F}\text{P}$ ratios was stressed. Most importantly, the value of titrating ANA for the diagnosis of the CTD was discussed. ANA titers higher than 1/500 are usually very significant clinically, often found in spontaneous or drug-induced SLE and few other CTD. The immunologic aspects of ANA and their potential value as aids in the diagnosis and management of the CTD were discussed. Anti-nDNA antibodies have been found to have a high degree of specificity for SLE and high titers of these antibodies correlate well with low levels of serum complement and severity of kidney involvement. The spectrum of ANA in the sera from patients with SLE has been expanded with the finding of anti-Sm antibodies which, when detected by gel precipitation with prototype serum, have been found so far only in SLE. Some of these antibodies have been found to have prognostic significance. Patients with MCTD and a group of patients with SLE have high titers of serum ANA with specificity for an RNase-sensitive component of ENA. The group of SLE patients defined by the presence of these antibodies (anti-Mo) have a better prognosis and in general develop only mild nephritis or have no kidney involvement at all. High titers of pure antinucleolar antibodies probably are found almost exclusively in the sera of patients with scleroderma. Some ANA have organ specificity, and GS-ANA have been found in all patients with Felty's syndrome and in a large proportion of patients with RA.One of the great advances in the field has been the recognition that ANA can be induced in the human and in experimental animals by the use of a number of therapeutic agents. Some of these agents can also induce a clinical picture resembling spontaneous SLE, though kidney involvement does not occur or is extremely mild. It is interesting that the whole spectrum of ANA can be found in drug-induced LE except anti-nDNA antibodies which have been associated to the pathogenesis of immune complex nephritis in spontaneous SLE.There is no doubt that research on ANA has contributed a great deal to the understanding of the CTD and will continue to be a valuable tool for the clinician and the investigator.     

Relationship of clinical findings in systemic lupus erythematosus to seroreactivity

We have characterized 52 consecutive patients fulfilling 4 or more of the American Rheumatism Association criteria for systemic lupus erythematosus in order to provide, for the first time, a homogeneous sample for statistical comparison of antinuclear antibody (ANA)-positive and ANA-negative groups. Ten patients (19%) were seronegative. There was no significant difference in age, disease activity, organ system involvement, erythrocyte sedimentation rate, immune complex levels, or C3 levels. The ANA-negative group showed a higher incidence of involvement for whites and men. Leukopenia, lower levels of antibody to DNA, and higher C4 levels were also characteristic of the ANA-negative group.     

Detection of anti-nuclear antibody by immunofluorescence assay and enzyme immunoassay in childhood systemic lupus erythematosus: experience from Bangladesh

Background: Systemic lupus erythematosus (SLE) is a multisystem, chronic but often episodic, autoimmune disease that is characterized by the presence of antinuclear antibodies (ANA). The criteria set by American College of Rheumatology are widely used for diagnosis of SLE. Elevation of ANA titer is the most sensitive of the ACR criteria. There are different methods for detection of ANA. Indirect immunofluorescence (ANA‐IFA) and enzyme immunoassay (ANA‐EIA) are commonly used methods. The sensitivity of ANA‐IFA using HEp‐2 cell substrate is 90–100% in systemic rheumatic diseases. In Bangladesh most of the laboratories use ANA‐EIA for detection of ANA. As the sensitivity of ANA‐EIA is lower than ANA‐IFA it might be that we are missing many cases of ANA positivity in childhood SLE cases. Objectives: To detect ANA by immunofluorescence assay using HEp‐2 cell substrate and enzyme immunoassay in childhood SLE and to compare the diagnostic performance of these methods. Material and methods: This is a cross‐sectional analytical study. A total of 40 patients were enrolled. Among them 20 were childhood SLE cases. Another 20 patients of childhood rheumatic diseases other than SLE were taken as the disease control group. Result: In childhood SLE cases, 100% were ANA‐positive by IFA and 55% were ANA positive by EIA. The sensitivity of ANA‐IFA was 100%. In contrast, sensitivity of ANA‐EIA was 55%. Conclusion: ANA‐IFA is superior to ANA‐EIA for detection of ANA in childhood SLE patients. ANA‐IFA should be the primary screening test for children with clinical features suggestive of SLE.     

Urinary excretion of antinuclear antibodies

The frequency of antinuclear antibodies (ANA), the immunoglobulin class of ANA and their specificity for known nuclear antigens were determined in 24-h urine collections from patients with systemic lupus erythematosus (SLE) and progressive systemic sclerosis (PSS). Sixteen % of SLE patients had detectable urine ANA by indirect immunofluorescence using mouse kidney substrate. A higher incidence, 32% of SLE and 28% of PSS patients, had detectable ANA in a titer greater than or equal to 1:16 using HEp-2 cell substrate. IgG ANA was the most frequent immunoglobulin class of antibodies present in the urine; 56% of SLE and 29% of PSS patients with urine ANA had more than one immunoglobulin class of antibodies. Antibodies to Sm, nRNP, SS-A and dsDNA were detected in SLE urine; antibodies to SS-A and centromere were detected in PSS urine. Urine ANA detected on mouse kidney substrate and urine dsDNA antibodies correlated with diffuse proliferative glomerulonephritis in patients with SLE. Sixty-two% of SLE patients with urine ANA had proteinuria. In the remaining SLE patients and in all the PSS patients with urine ANA however, protein excretion was normal. SDS-PAGE revealed heavy and light immunoglobulin molecules in both SLE and PSS patients with urine ANA. The intact immunoglobulin was shown to have ANA activity. ANA present in the urine of SLE and PSS patients with apparently normal renal function may be an early sign of altered glomerular capillary membrane permeability.     

Opsonization of late apoptotic cells by systemic lupus erythematosus autoantibodies inhibits their uptake via an Fcgamma receptor-dependent mechanism

OBJECTIVE: Decreased clearance of apoptotic cells is suggested to be a major pathogenic factor in systemic lupus erythematosus (SLE). The aim of this study was to investigate whether the binding of SLE autoantibodies to apoptotic cells influences the phagocytosis of these cells by macrophages. METHODS: Apoptosis was induced in a human T cell line (Jurkat) and a keratinocyte cell line (HaCaT) by ultraviolet B irradiation. Binding of purified IgG from 26 SLE patients and 15 healthy controls to apoptotic cells was assessed by flow cytometry and Western blotting. Phagocytosis of IgG-opsonized apoptotic cells by monocyte-derived macrophages was assessed by light microscopy. Similar experiments were performed with a monoclonal antibody against SSA/Ro and IgG fractions from 5 patients with Sj?gren's syndrome (SS) and 5 patients with rheumatoid arthritis (RA). RESULTS: IgG fractions from all 26 SLE patients bound to late apoptotic, but not early apoptotic, cells. IgG fractions isolated from SLE patients with different autoantibody profiles showed comparable levels of binding. IgG fractions from healthy controls did not bind. Opsonization of apoptotic cells with IgG fractions from SLE patients resulted in a significant inhibition of phagocytosis as compared with healthy control IgG fractions. A monoclonal antibody directed against SSA/Ro and IgG isolated from 5 antinuclear antibody (ANA)-positive patients with SS were also able to elicit these effects, whereas IgG from 5 ANA-negative patients with RA did not. The inhibitory effect of patient IgG was abolished by blocking either the Fcgamma receptors (FcgammaR) or the constant region of IgG, using a specific Fc-blocking peptide. CONCLUSION: Autoantibodies from SLE patients are able to opsonize apoptotic cells and inhibit their uptake by macrophages via an FcgammaR-dependent mechanism.     

Antibodies to cytoplasmic antigens in lupus erythematosus

Seven patients with classic cutaneous lupus ery-thematosus are described. Three of these patients had features satisfying four of the American Rheumatism Association (ARA) preliminary criteria for the diagnosis of systemic lupus erythematosus (SLE). Their sera, however, lacked antinuclear antibodies but demonstrated precipitating antibodies reactive against cytoplasmic RNP (La) and non-nucleic acid (Ro) antigens. Four additional ANA-negative patients lacking significant skin disease but having a lupus-like multisystem disease were found to have antibodies to soluble cytoplasmic antigens. Thirty-three of 130 ANA-positive SLE patients, but none of 16 discoid lupus patients, possessed these anticytoplasmic antibodies. These findings suggest that antibodies to Ro and La may be a marker for systemic disease in ANA-negative patients with 1) cutaneous lupus and 2) a distinct sub-population of patients with a lupus-like syndrome without skin disease.