Cutaneous Neonatal Lupus Research Articles

IVIG Does Not Prevent Neonatal Lupus Erythematosus–Associated Heart Block

As previously reported, mothers of neonates with cutaneous or cardiac neonatal lupus (NL) have an increased risk for development of congenital heart

Cutaneous manifestations of neonatal lupus and risk of subsequent congenital heart block.

Cutaneous disease associated with placental transport of maternal anti-SSA/Ro or anti-SSB/La antibodies is transient, and children often appear to be otherwise healthy. However, the impact of this manifestation of neonatal lupus (NL) on the risk of cardiac disease occurring in a future pregnancy is critical for family counseling and for powering preventive trials. The purpose of this study was to determine the recurrence rates of NL, with specific focus on cardiac NL following cutaneous NL in a child enrolled in the Research Registry for Neonatal Lupus (RRNL). Fifty-eight families who were enrolled in the RRNL met the following inclusion criteria for our study: maternal anti-SSA/Ro or anti-SSB/La antibodies, a child with cutaneous NL, and a pregnancy subsequent to the child with cutaneous NL. The majority of the 58 mothers (78%) were Caucasian. Of 77 pregnancies that occurred following the birth of a child with cutaneous NL, the overall recurrence rate for any manifestation of NL was 49% (95% confidence interval [95% CI] 37-62%); 14 pregnancies (18.2%) were complicated by cardiac NL, 23 (29.9%) by cutaneous NL, and 1 (1.3%) by hematologic/hepatic NL. A subset analysis was restricted to the 39 children who were born after the initial child with cutaneous NL had been enrolled in the RRNL. The overall recurrence rate for NL was 36% (95% CI 20-52%); 5 pregnancies (12.8%) were complicated by cardiac NL and 9 (23.1%) by cutaneous NL. There were no significant differences in the following maternal risk factors for having a subsequent child with cardiac or cutaneous NL: age, race/ethnicity, anti-SSB/La status, diagnosis, use of nonfluorinated steroids, or breastfeeding. The sex of the subsequent fetus did not influence the development of cardiac or cutaneous NL. Based on data from this large cohort, the identification of cutaneous NL in an anti-SSA/Ro antibody-exposed infant is particularly important, since it predicts a 6-10-fold risk of a subsequent child developing cardiac NL.

An asymptomatic mother of cutaneous neonatal lupus child was diagnosed with Sjoegren's syndrome suspected

We report an asymptomatic mother of a cutaneous neonatal lupus child was diagnosed with Sjögren's syndrome suspected after parturition. A 30-year old woman was visited our hospital to evaluated autoimmune disease because her baby was diagnosed as cutaneous neonatal lupus. Both gum test and Schirmer's test were positive. Antinuclear antibody, anti-SS-A and anti-SS-B antibody were positive. Serum IgG was elevated (2918 mg/dl). Finally, this case was suspected as Sjögren's syndrome. Continuoues follow-up of asymptomatic mothers of a neonatal lupus child is warranted.

Cutaneous neonatal lupus erythematosus with unusual features

A three month-old boy was brought by his mother with complaints of multiple reddish lesions on his trunk and face since birth. The patient had erythematous annular plaques with scaling on his extremities, palms and soles with periorbital erythema and edema giving the characteristic "eye mask" or "owl's eye" appearance. His mother did not have history of any illness. Hemogram, liver and renal function tests were within normal limits. A skin biopsy was suggestive of subacute cutaneous lupus erythematosus. Immunological work-up was positive for antinuclear antibodies (ANA) (1:40) with anti-Ro titers of 3.4 and 3.47 (>1.1 = clinically significant titre) in the mother and child respectively, although negative for anti-La antibodies. The child's electrocardiogram and 2D echocardiography were normal. We are presenting a case of anti-Ro-positive cutaneous lupus erythematosus with an uncommon skin manifestation.

Anti-Ro/SSA and La/SSB antibodies

The Ro/La system is considered as an heterogeneous antigenic complex, constituted by three different proteins (52 kDa Ro, 60 kDa Ro and La) and four small RNAs particles. Anti-Ro/SSA are the most prevalent specificity among many autoimmune diseases, such as systemic lupus erythematosus (SLE), SS/SLE overlap syndrome, subacute cutaneous LE (SCLE), neonatal lupus and primary biliary cirrhosis. In contrast, anti-La/SSB is more associated with Sjögren's syndrome (SS). The differences between 52 kDa, 60 kDa Ro and La could explain why different assays did not show equivalent performance in anti-Ro and anti-La autoantibodies detection. The RNA precipitation assay had the highest sensitivity and specificity, usually considered as the reference methods. CIE is considered the most reliable to detect anti-Ro/SSA antibodies in routine practice, performing better than immunoblotting (IB) and some ELISAs. It shows a high sensitivity (89%) and specificity (100%). ELISA is generally considered a safe, rapid, sensitive and specific tecnique. Therefore, its high sensitivity often corresponds to a very low clinical specificity and the assay can give false positive results. Therefore, it is very important to search anti-Ro and anti-La only in selected patients, using the assay with high specificity and good predictive value, in order to have clinically significant and true positive results.

Genetic association of cutaneous neonatal lupus with HLA class II and tumor necrosis factor alpha: implications for pathogenesis.

Cutaneous neonatal lupus resembles subacute cutaneous lupus erythematosus (SCLE), and photosensitivity is a common symptom. Tumor necrosis factor alpha (TNFalpha) release by ultraviolet light-exposed keratinocytes may be exaggerated in SCLE patients who have the haplotype TNFalpha -308A;DRB1*03. Accordingly, this study was undertaken to seek genetic and histologic evidence for a role of TNFalpha in the pathogenesis of cutaneous neonatal lupus. DNA was isolated from 83 children (22 with rash, 35 with congenital heart block [CHB], 26 unaffected siblings) and 58 mothers from the Research Registry for Neonatal Lupus. The -308A allele (associated with higher TNFalpha production), HLA-DRQB1*02, and HLA-DRB1*03 were each present in the majority of children with rash (64%, 68%, and 64%, respectively). The frequency of all 3 6p alleles occurring together in 1 individual was greater in children with rash than in children who had either CHB or no manifestation of neonatal lupus (59% versus 30%; P = 0.02). This association with neonatal lupus rash was equivalent to published findings in a cohort of patients with SCLE, but significantly greater than the association in patients with discoid lupus erythematosus. Prominent TNFalpha staining in the epidermis was observed in lesional skin from 3 children with rash, but not in skin from a healthy neonate. Taken together, the finding of a genetic predisposition to generate increased levels of TNFalpha following tissue injury and the histologic demonstration of TNFalpha in the target organ support the notion that this inflammatory cytokine plays a role in the pathogenesis of cutaneous neonatal lupus. Furthermore, the results of these studies provide evidence of a biologic link between neonatal lupus and the rash of SCLE.

Relationship of maternal autoimmune response to clinical manifestations in children with congenital complete heart block.

To study the autoimmune response in mothers of children with congenital heart block (CHB) diagnosed at different ages and with different clinical manifestations. Clinical data and sera for the determination of immunological tests were available from 104 mothers of 113 children born between 1950 and 2000 and diagnosed with CHB before the age of 16 y. Prenatal diagnosis was performed in 74 (65%) children of 65 mothers, and 39 (35%) children had postnatal diagnosis of CHB. Maternal antibodies to 52 kd and 60 kd SS-A, and to 48 kd SS-B were determined by time-resolved fluoroimmunoassay (TR-FIA) and to antinuclear antibodies (ANA) by immunoflurescense (IF). Out of the 65 mothers of children with in utero diagnosed CHB, 88% had antibodies to 52 kd SS-A and 83% had ANA. Antibodies to 60 kd SS-A and 48 kd SS-B were less frequently present, in 48% and in 54% of the mothers, respectively. Seven (11%) of the mothers were negative by all immunoassays. Of the 13 mothers of children with in-infancy diagnosed CHB, one mother had high-titer ANA. After 1 y of age, CHB was diagnosed in 26 children; at 1 to 6 y in 16 and after 7 y in 10 children; 1/16 and 1/10 patients had positive antibodies. In all twin pregnancies (n = 4) and in all families with recurring cases of CHB (n = 5), maternal antibodies were positive in at least one assay. The titer of 48 kd anti-SS-B antibodies was significantly higher in children with cutaneous neonatal lupus (98.1 vs 41.0; p = 0.02). All mothers whose children died before the age of 4 y (n = 8) and 85% (11/13) of mothers whose children developed cardiomyopathy had elevated antibody titers in at least one assay. However, we could not find any prognostic value of maternal antibody levels or specificities on the clinical outcome of the children with CHB. Although rare, late detection or postnatal progression of CHB in antibody-mediated CHB should be taken into consideration. Maternal antibody levels or specificities have prognostic effect neither on the clinical outcome of the child with CHB nor on the risk of reappearance in the same family.

Fetal Echocardiographic Screening of Pregnancies of Mothers with Anti-Ro and/or Anti-La Antibodies

The objectives of this study are to assess the incidence of congenital complete heart block (CCHB) in pregnant women who are anti-Ro and/or La positive. Between January, 1988 and July 1997, 118 pregnancies in 105 women were assessed by fetal echo at 18, 24, and 32 weeks' gestation. Of these 105, 96 had no history of a previous fetus with CCHB; 11(12 pregnancies) a history of a pregnancy with CCHB; and 4 a previous child with cutaneous neonatal lupus erythematosus (CNLE). The 102 pregnancies in 96 women with anti-Ro and/or anti-La antibodies and no history of a previous child with NLB, resulted in 100 live-births with no CCHB. There was 1 dilated cardiomyopathy at 6 months, 1 child with CCHB, and 1 with sclerosis of the endocardium. No case of CCHB was observed in 102 pregnancies without a previous history of CCHB. These results suggest that the risks of CCHB, without a prior history are low.

Cutaneous Neonatal Lupus Without Heart Block: Risks for Mother, Infant, and Future Siblings

Rheumatology| February 01 2001 Cutaneous Neonatal Lupus Without Heart Block: Risks for Mother, Infant, and Future Siblings AAP Grand Rounds (2001) 5 (2): 10. https://doi.org/10.1542/gr.5-2-10 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter LinkedIn Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Cutaneous Neonatal Lupus Without Heart Block: Risks for Mother, Infant, and Future Siblings. AAP Grand Rounds February 2001; 5 (2): 10. https://doi.org/10.1542/gr.5-2-10 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search nav search search input Search input auto suggest search filter All PublicationsAll JournalsAAP Grand RoundsPediatricsHospital PediatricsPediatrics In ReviewNeoReviewsAAP NewsAll AAP Sites Search Advanced Search Topics: heart block, neonatal lupus erythematosus, relationship - sibling You do not currently have access to this content.

The health of mothers of children with cutaneous neonatal lupus erythematosus differs from that of mothers of children with congenital heart block

PURPOSE: Neonatal lupus erythematosus is caused by the transplacental passage of maternal autoantibodies. The aim of this study was to determine the risk of connective tissue disorders in mothers of children with cutaneous neonatal lupus erythematosus, as compared with the risk in mothers of children with congenital heart block, which is also often caused by maternal autoantibodies. SUBJECTS AND METHODS: We prospectively studied all mothers of children with cutaneous neonatal lupus erythematosus during a 14-year period at the Hospital for Sick Children, Toronto, Ontario, Canada. We identified 28 mothers, of whom 24 were eligible for study. The health and antibody status of the mothers were determined at the birth of the child and at follow-up. RESULTS: All mothers had anti-Ro antibodies at the time of birth. Initially 10 mothers were healthy and 14 mothers had either a defined (n = 9) or an undifferentiated (n = 5) autoimmune disorder. At a mean follow-up of 7 years, 13 (1 of whom had died) had a defined connective tissue disease, and 5 had an undifferentiated autoimmune disorder. Only 6 (25%) remained asymptomatic. By comparison, 36 (56%) of 64 mothers of children with congenital heart block were asymptomatic at follow-up ( P <0.005). CONCLUSIONS: The majority of mothers of children with cutaneous neonatal lupus erythematosus had a defined or undifferentiated autoimmune disorder at the time of the child’s birth, and others developed these conditions during follow-up. The health of these mothers appears to differ from that of mothers of children with congenital heart block.

The clinical spectrum of anti-Ro-positive cutaneous neonatal lupus erythematosus

Background: Cutaneous neonatal lupus erythematosus (NLE) is an uncommon disease described mainly through isolated case reports. Objective: Our purpose was to examine the cutaneous spectrum, clinical associations, and course of disease in babies with anti-Ro-positive NLE. Methods: This is a retrospective case series evaluation of newborns with anti-Ro-positive NLE seen at a single ambulatory care university center over a 20-year period. Cases were drawn from a population of 3.2 million. Follow-up was at least 3 years. Results: Four boys and 14 girls were included in our evaluation. Distribution of skin lesions in 18 babies was as follows: face, 17; periorbital “owl-eye” or “eye mask” facial rash, 14; scalp, 15; arms and legs, 13; trunk and groin, 6. Crusted lesions were predominant in 3. Photosensitivity was seen in 12, and features of cutis marmorata telangiectasia congenita were observed in 4. In 17 neonatal lupus was not suspected until the dermatology consultation. Noncutaneous manifestations included thrombocytopenia in 4, cholestatic hepatitis in 3, and congenital heart block in 3. Four patients had residual telangiectasia that persisted for 3 or more years but eventually cleared in 2 patients. Three babies had dyspigmentation that spontaneously cleared within 22 months. None had atrophy or scarring. Conclusion: Periorbital, scalp, and extremity lesions are common in cutaneous NLE. Crusted lesions predominated in male infants. In children selected by cutaneous involvement, thrombocytopenia and hepatic disease were present as frequently as cardiac disease and occurred more frequently in male babies with crusted skin lesions. Children with cutaneous NLE should be evaluated for hematologic and hepatic as well as cardiac involvement.(J Am Acad Dermatol 1999;40:675-81.)

Antinuclear antibody-keratinocyte interactions in photosensitive cutaneous lupus erythematosus.

Autoimmune diseases are characterized by various circulating autoantibodies, especially antinuclear antibodies (ANA). It has been a long-standing issue as to whether and/or how ANA interact with epidermal cells to produce skin lesions. Of these ANA, the anti-SS-A/Ro antibody is the most closely associated with photosensitivity in patients with systemic lupus erythematosus (SLE) and its subgroups, including subacute cutaneous lupus erythematosus (SCLE) and neonatal lupus erythematosus (NLE). SS-A/Ro antigens are present in the nucleus and cytoplasm, and interestingly, ultraviolet B (UVB) light translocates these antigens to the surface of the cultured keratinocytes. Thus, anti-SS-A/Ro antibodies in the sera can bind to the relevant antigens expressed on the UVB-irradiated keratinocyte surface, and have been speculated to be an important inducer of antibody-dependent keratinocyte damage. This interaction between the anti-SS-A/Ro antibodies and UVB-irradiated keratinocytes may induce the skin lesions through a cytotoxic mechanism. This review will focus on the involvement of antibody-dependent cellular cytotoxicity in the pathogenesis of the skin lesions observed in photosensitive cutaneous lupus erythematosus.

Outcome of planned pregnancies in systemic lupus erythematosus: a prospective study on 62 pregnancies.

We conducted a prospective study in order to determine planned pregnancy outcome in systemic lupus erythematosus followed in a tertiary referral centre. Pregnancy was authorized if disease was inactive on 20 mg/day prednisone or less for at least 1 yr. Upon the diagnosis of pregnancy, systematic corticosteroids consisting of 10 mg/day prednisone or more were started. In the case of antiphospholipid antibodies, 100 mg/day aspirin was added, replaced by heparin in the pre-partum period. In the case of antiphospholipid syndrome complicated by previous thrombotic events or fetal losses despite aspirin, heparin was prescribed. One woman with a history of atrioventricular block was treated with dexamethasone. Patients were monitored by medical and obstetrical examination, and laboratory tests carried out at least monthly and a quarterly echography. Among 62 pregnancies in 38 women, lupus flare was observed in 27% of the cases, 6% of which occurred in the post-partum period. Flares were moderate except in one renal involvement in a woman with prior diffuse proliferative glomerulonephritis. Therapy was not modified in half of the cases. Pregnancy ended in early spontaneous abortion not related to lupus flare (n = 10), stillbirth (n = 2). induced abortion (n = 2), preterm birth (n = 29) and full-term birth (n = 19). Caesarean section was performed in nine cases. A severe infection occurred in two premature neonates. Another premature neonate was growth retarded. Two children had cutaneous neonatal lupus. No child died, neither had atrioventricular block. Stillbirth and severe prematurity were more common in mothers with antiphospholipid syndrome. After exclusion of early spontaneous and induced abortions, the live birth rate was 96%, that is close to the French general population. The main problem remains a high rate of prematurity, but without maternal or neonatal death.

Disparate Locations of the 52- and 60-kDa Ro/SS-A Antigens in Cultured Human Keratinocytes

Anti-52- and anti-60-kDa Ro/SS-A (Ro) autoantibodies are produced by most patients with subacute cutaneous lupus erythematosus and neonatal lupus erythematosus and are thought to be pathogenic in these two disorders. To learn more about the epidermal antigens targeted by Ro autoantibodies, a panel of anti-52 and anti-60-kDa Ro antibodies was purified from human autoimmune sera and rabbit antisera and then used to: (i) determine the expression and location of the Ro antigens in human keratinocytes; (ii) clarify discrepancies in previous localization studies; and (iii) verify the existence of Ro autoantibodies that cross-react with the 52- and 60-kDa Ro antigens, as previously reported. By immunoblot analysis these antibodies demonstrate that 52- and 60-kDa Ro proteins are expressed in normal human skin and cultured keratinocytes. By indirect immunofluorescence studies with cultured human cells, the anti-52-kDa Ro antibodies produce fine granular cytoplasmic fluorescence and less intense nuclear fluorescence, with apparent nucleolar sparing. The anti-60-kDa Ro autoantibodies produce weak cytoplasmic fluorescence and intense coarse granular nuclear fluorescence with apparent nucleolar sparing. We found distinct differences in the intracellular localization of the 52- and 60-kDa Ro autoantigens. This difference suggests that the 52-and 60-kDa Ro antigens may have independent cellular functions. Finding 60-kDa Ro antigen predominantly in the nucleus challenges the notion that the majority of the intracellular 60-kDa Ro antigen is complexed with the cytoplasmic hY RNA. Additionally, our failure to find a cross-reactive epitope on these two proteins indicates that the 52-kDa Ro antigen is probably a true immunogen and not merely a protein that cross-reacts with anti-60-kDa Ro autoantibodies, as others have suggested.

The Recognition of Human 60-kDa Ro Ribonucleoprotein Particles by Antibodies Associated With Cutaneous Lupus and Neonatal Lupus

The hY RNAs form a macromolecular complex with the 60-kDa Ro protein and may in addition be bound by the La protein. In this study, we examine the autoantibody responses to the intact protein-RNA complexes in 18 subacute cutaneous lupus (SCLE), 10 discoid lupus (DLE), and 18 neonatal lupus erythematosus (NLE) sera. All SCLE and NLE serum samples precipitated all four of the Ro hY RNAs, whereas none of the DLE serum samples precipitated the hY RNAs. Among the SCLE and NLE sera, there was a significant association between the amount of Ro hY RNAs precipitated and the concurrent presence of anti-La antibodies in the sera (p = 0.008), consistent with the hypothesis that both the 60-kDa Ro and the La proteins can bind the Ro hY RNAs. There was no correlation between the amount of hY RNAs precipitated and the titer of antibodies to the 60-kDa Ro protein in enzyme-linked immunosorbent assay (ELISA). This may be due to a difference in the epitopes formed by the antigen in the respective assays. The autoantibody response to Ro in SCLE and NLE, which is generally detectable by both immunodiffusion and ELISA, is directed to all the subsets of the Ro protein-hY RNA complexes. The autoantibody response in DLE, though frequently detectable by ELISA, is not of sufficient concentration or affinity to precipitate the Ro protein-RNA complexes. The autoantibody response to Ro in SCLE and NLE may include antibodies to epitopes created by the complexing of the 60-kDa Ro protein with hY RNA.

Calreticulin is transcriptionally upregulated by heat shock, calcium and heavy metals

Calreticulin is a new human rheumatic disease-associated autoantigen that plays a multifaceted role in cell biology. In earlier studies, this protein was shown to share an intimate relationship with the Ro SS-A autoantigen complex, although the nature of this association continues to be debated. Since modulation of the Ro SS-A autoantigen in epidermal keratinocytes has been implicated in the pathogenesis of subacute cutaneous lupus erythematosus and neonatal lupus erythematosus, we have begun to examine the transcriptional regulation of calreticulin. A 504 bp calreticulin promoter fragment was subcloned into a reporter gene plasmid containing firefly luciferase. Calcium ionophore, heat shock, and heavy metals such as zinc and cadmium were consistently found to increase calreticulin transcriptional activities in A431 cells (a human epidermoid squamous carcinoma cell line) under transient transfection conditions. These studies suggest that (a) calreticulin is regulated at the transcriptional level, and (b) calreticulin, like some other LE-related autoantigens, appears to function as a heat shock/stress-response gene.

Pathomechanisms of Photosensitive Lupus Erythematosus

This review discusses the mechanisms involved in different photosensitive lupus syndromes: acute cutaneous lupus erythematosus, chronic cutaneous (discoid) lupus erythematosus, subacute cutaneous lupus erythematosus, and neonatal lupus erythematosus. It is proposed that there are three principal determinants of photosensitivity in lupus: 1) susceptibility to UVR-induced release of epidermal and dermal cytokines; 2) susceptibility to UVR-induced release or translocation of sequestered antigens in the epidermis or dermis; and 3) different specific immunologic effector mechanisms, activated by cytokines and directed against discrete epidermal targets. Several characteristics of photosensitive lupus are discussed in detail: autoantibody specificities, autoantigen translocation, induction of epidermal intercellular adhesion molecule-a (ICAM-1), vascular activation, cytokine release and T-cell activation, and clinical phototesting. The role of antibodies to the extractable nuclear antigens Ro and La and the relationship to subacute cutaneous lupus erythematosus (SCLE) and neonatal lupus erythematosus is discussed in detail, and a model of SCLE is proposed.

Pathomechanisms of photosensitive lupus erythematosus.

This review discusses the mechanisms involved in different photosensitive lupus syndromes: acute cutaneous lupus erythematosus, chronic cutaneous (discoid) lupus erythematosus, subacute cutaneous lupus erythematosus, and neonatal lupus erythematosus. It is proposed that there are three principal determinants of photosensitivity in lupus: 1) susceptibility to UVR-induced release of epidermal and dermal cytokines; 2) susceptibility to UVR-induced release or translocation of sequestered antigens in the epidermis or dermis; and 3) different specific immunologic effector mechanisms, activated by cytokines and directed against discrete epidermal targets. Several characteristics of photosensitive lupus are discussed in detail: autoantibody specificities, autoantigen translocation, induction of epidermal intercellular adhesion molecule-a (ICAM-1), vascular activation, cytokine release and T-cell activation, and clinical phototesting. The role of antibodies to the extractable nuclear antigens Ro and La and the relationship to subacute cutaneous lupus erythematosus (SCLE) and neonatal lupus erythematosus is discussed in detail, and a model of SCLE is proposed.

IgG Subclasses in the Serum and Skin in Subacute Cutaneous Lupus Erythematosus and Neonatal Lupus Erythematosus

IgG subclasses differ in their biologic and chemical properties, such as complement fixation, protein and cellular binding, and placental transfer. In this study, IgG subclasses of anti-Ro/SSA antibodies in subacute cutaneous lupus (SCLE) and neonatal lupus (NLE) are examined in the serum and in the skin. IgG subclasses in NLE beginning in utero (NLE-heart disease) are compared to subclasses in NLE beginning after birth (NLE-skin disease). Human skin was grafted onto athymic mice, mice were injected with one of eight anti-Ro/SSA maternal NLE sera (four heart block, four skin disease) or seven anti-Ro/SSA SCLE sera, and grafts were examined for IgG subclasses using monoclonal anti-human IgG subclass reagents in an immunofluorescent technique. Lesional skin was examined from four SCLE patients. IgG1 was the only IgG subclass detected in the grafts and skin lesions. IgG1 was the predominant anti-Ro/SSA IgG subclass detected in SCLE and NLE sera in an ELISA using a synthetic Ro/SSA polypeptide. These studies show that the maternal anti-Ro/SSA autoantibodies in NLE-heart disease sera are predominantly IgG1 and are therefore likely to be present in the fetus at the time of gestation, when heart block usually develops. Second, differences in the clinical presentations of NLE (in utero vs. postnatal disease) cannot be attributed to differences in anti-Ro/SSA IgG subclasses. Finally, the subclass bound in the skin in SCLE is IgG1, a subclass capable of mediating tissue injury via complement or cellular effectors.

Estradiol enhances binding to cultured human keratinocytes of antibodies specific for SS-A/Ro and SS-B/La. Another possible mechanism for estradiol influence of lupus erythematosus.

A strong association between anti-SS-A/Ro and anti-SS-B/La antibodies and skin lesions has been well documented in subacute cutaneous lupus erythematosus and neonatal lupus erythematosis in which 70 to 80% of patients are female. In order to better understand the mechanisms of the influence of sex hormones on cutaneous lupus, we designed immunopathological in vitro experiments to evaluate the effects of estradiol and other sex steroids on the binding of SS-A/Ro- and SS-B/La-specific antibodies to cultured human keratinocytes from neonates. Cultured human keratinocytes incubated with antisera specific for SS-A/Ro or SS-B/La Ag were fixed with either acetone or paraformaldehyde and then analyzed in indirect immunofluorescent assays or by FACS analysis to detect cell surface IgG binding as an indirect measure of SS-A/Ro and SS-B/La Ag expression on the cell surface of keratinocytes. Estradiol (10(-5) to 10(-7) M) augmented binding of antiserum probes on the surface of cultured keratinocytes, with 10(-7) M estradiol showing the highest induction of cell surface binding of antisera specific for SS-A/Ro plus SS-B/La Ag (24.5% of cells were positive). In contrast, dihydrotestosterone, testosterone, and progesterone showed no augmentation. The augmentation by estradiol was partially inhibited by the antiestrogen nafoxidine. Estradiol augmented the relative incidence and absolute number of small or cuboidal cells binding antibodies specific for SS-A/Ro and SS-B/La Ag, whereas the number and incidence of larger differentiated cells binding anti-SS-A/Ro and anti-SS-B/La decreased significantly in cell cultures stimulated with estradiol. Flow cytometric analysis utilizing monospecific anti-SS-A/Ro or anti-SS-B/La sera showed that estradiol induced binding of anti-SS-A/Ro in 13.1% of cultured keratinocytes, of anti-SS-A/La in 14.4%, and of sera specific for both Ag in 21.4%. This direct association between estradiol and the augmentation of binding to the cell surface of human keratinocytes of IgG from antisera specific for SS-A/Ro and SS-B/La Ag may be a trigger factor of immunologic damage in lupus and may be important in the different sex rates observed in skin manifestation of subacute cutaneous and neonatal lupus erythematosis.