Systemic Lupus Erythematosus Skin Lesions Research Articles

IL-1β mediated fibroblast-neutrophil crosstalk promotes inflammatory environment in skin lesions of SLE

Systemic lupus erythematosus (SLE) is characterized by immune dysregulation, with neutrophil infiltration in skin lesions contributing to inflammation and disease progression. However, the interaction between fibroblasts and neutrophils in SLE skin lesions has not been fully explored. Using single-cell RNA sequencing, we identified a unique CXCL1+ fibroblast subset in SLE lesions. We found that CXCL1+ fibroblasts recruit and activate neutrophils, increasing the production of inflammatory mediators, reactive oxygen species, and neutrophil extracellular traps. These fibroblasts also facilitated the transition of neutrophils to a low-density phenotype. Notably, these fibroblasts delayed neutrophil apoptosis, extending their survival and amplifying inflammation. Serum amyloid A1, secreted by CXCL1+ fibroblasts, emerged as a key activator of neutrophils. Activated neutrophils, in turn, secreted IL-1β to induce CXCL1+ fibroblast differentiation via activating the NF-κB pathway. In conclusion, our findings reveal that IL-1β-induced CXCL1+ fibroblasts significantly modulate pro-inflammatory neutrophils, underscoring the critical crosstalk between fibroblasts and neutrophils in SLE pathogenesis.

Oxysterols contribute to immune cell recruitment in SLE skin lesions

BackgroundAbnormal oxysterol metabolism has been observed in the peripheral blood of SLE patients, but its role in systemic lupus erythematosus (SLE) skin lesions remains unclear.MethodsTargeted oxidized lipid metabolomics analysis using liquid chromatography-mass spectrometry (LC-MS) was performed to quantify oxysterols in SLE skin lesions. Immunohistochemical staining and single-cell sequencing data analysis confirmed the upregulation of oxysterol-encoding enzymes CH25H and CYP7B1. The impact on fibroblast-mediated PBMCs chemotaxis was assessed using a transwell chamber.ResultsWe identified aberrant oxidized cholesterol metabolism in SLE skin lesions, characterized by elevated levels of 7-ketocholesterol, 5α-6α-cholestane-3β,5α,6β-triol, and so on. Fibroblasts were the primary cells expressing oxysterol-encoding genes, with CH25H and CYP7B1 expression upregulated via the IL-1β-mediated p38 MAPK and NFκB pathways. Notably, IL-1β-stimulated fibroblasts demonstrated enhanced PBMCs recruitment, which was attenuated by a GPR183 inhibitor.ConclusionOur findings reveal a potential mechanism by which fibroblasts contribute to immune cell recruitment in SLE skin lesions by expression of CH25H and CYP7B1. This study underscores the significance of oxysterol metabolism in SLE skin lesion pathogenesis and highlights potential therapeutic targets for SLE skin lesion treatment.Graphical abstract

Dermatological Manifestation of SLE Patients, Living in Aseer Region.

Systemic lupus erythematosus (SLE) is an autoimmune disease that affects both men and women differently and has a variety of multisystemic symptoms. One of the diseases most often affected target organs is the skin. Different ethnic and racial groupings may display variations in disease incidence, clinical heterogeneity, and severity depending on environmental, cultural, or genetic factors. This study is conducted to determine the prevalence of SLE's cutaneous symptoms and their relationship to organ involvement. Data were gathered for this study from the patient chart, the study design was the retrospective chart review after the consent of the patients and obtaining an ethical approval, The study was carried out in Aseer Central Hospital, Abha Saudi Arabia. Out of a total of 100 patients 92% were females while 8% were males. The mean (SD) of the age of the respondent was 38.3 (8.5). 89.2 of the respondents had skin manifestations. A thorough understanding of SLE skin lesions will aid in the accurate identification of the condition and in the effective therapy of lupus patients. In order to more accurately diagnose cutaneous lesions in SLE patients, we need more dermatology and rheumatology clinics that combine expertise together.

Clinical variants of skin and mucous membrane lesions in systemic lupus erythematosus with juvenile onset

Skin and mucous membrane lesions are frequently seen in systemic lupus erythematosus (SLE) with the juvenile onset (juSLE), and they are extremely diverse. Skin manifestations can be the initial sign of the disease, they often respond first to adequate therapy, and recurrence or the appearance of a new type of lesions is the earliest indicator of exacerbation in many patients. In severe cases, skin lesions can lead to irreversible cosmetic defects, significantly affecting the quality of life. The article presents the clinical manifestations of various variants of skin and mucous membrane lesions in SLE with a debut in childhood and adolescence, their recognition is important for the timely diagnosis of SLE, as well as the correction of therapy for an existing disease, which improves the long-term prognosis and quality of life of patients.

An Enhanced Expression Level of CXCR3 on Tfh-like Cells from Lupus Skin Lesions Rather Than Lupus Peripheral Blood

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease, and the etiopathogenesis is unclear. Follicular helper T (Tfh) cells have been reported as an important pathogenic cell type in SLE. CXCR3 was reported to be decreased on lupus peripheral CD4+T cells. However, the expression level of CCR4, CCR6 and CXCR3 on Tfh-like cells in SLE peripheral blood and skin lesions is unknown. In this study, we detected CCR4, CCR6 and CXCR3 expression level on Tfh-like cells in the peripheral blood and skin lesions from SLE patients and normal controls (NCs). A decreased expression level of CXCR3 on Tfh-like cells was found in lupus peripheral blood. However, an increased CXCR3 expression was observed on total CD4+T and Tfh-like cells from lupus skin lesions. Moreover, we observed a higher expression level of CXCR3 in Tfh cells from human tonsils. These findings indicate that CXCR3 might help Tfh-like cells to migrate into the inflammatory sites.

Disordered cutaneous microbiota in systemic lupus erythematosus

The correlation between systemic lupus erythematosus (SLE) and microbiota colonization has been receiving much attention during recent years. Here, we screened the cutaneous bacterial spectrums of 69 SLE patients, 49 healthy controls and 20 dermatomyositis (DM) patients and identified the specific changes of cutaneous microbial composition and abundance in SLE patients. We observed the decreasing diversity in community richness and evenness and the greater heterogeneity in SLE patients compared to healthy controls, which were also different from the cutaneous microbiome of DM patients. The skin microbial community disorders in SLE patients were correlated with several clinical features such as serum low complement level, gender, renal involvement and myositis. According to the Kruskal-Wallis (KW) test, receiver operating characteristic (ROC) curve and LDA Effect Size (LEfSe) analysis, several bacterial taxa such as Staphylococcus, especially Staphylococcus aureus and Staphylococcus epidermidis, were identified to be potential markers for SLE skin lesions. Furthermore, Picrust analysis showed that Staphylococcus aureus infection pathway was significantly enriched and exhibited a strong correlation with genus Staphylococcus in SLE patients. The changes in the composition and abundance of cutaneous microbiota in SLE patients suggest that the microbial dysbiosis is associated with the pathogenesis of SLE, which may be potentially reliable biomarker or therapeutic target for SLE.

083 Increased T follicular helper-like cells and tertiary lymphoid structures in the skin lesions of discoid lupus erythematosus

Lupus erythematosus (LE) is an autoimmune disease with a broad clinical spectrum ranging from cutaneous lesions to severe systemic manifestations. Clinically, lupus patients with skin lesions can be divided into two subsets based on the organs involved: cutaneous LE (CLE), such as discoid LE (DLE), and systemic LE (SLE), e.g., acute LE (ACLE). Interestingly, the excessive production of autoantibodies can be found in serum and skin lesions of SLE, however, increased autoantibodies appear in skin lesions rather than serum of DLE. By now the pathomechanism of immune deposition in DLE remains unclear. Herein, with Multiplex immunofluorescence microscopy, in over half of 112 DLE biopsies, lymphoid aggregates ranged from tight clusters of B cells and T cells to highly organized structures that comprise functional germinal centres (GCs) (In 58% of cases (66/112), there were well-circumscribed aggregates of CD19+ B cells with CD4+ T cells. In 8% of biopsies (10/112), structures similar to GCs of human tonsil were observed.). Moreover, compared with SLE, the percentage of T cells in DLE showed no statistical difference (n=20, P=0.158), but the percentage of B cells was significantly higher in DLE (n = 20, P=0.0022). 5 samples were selected respectively from two group of LE to detect the proportions of Tfh cells (CD4/IL21/BCL6/PD-1/CXCR5). Then we found a significantly increased population of T follicular helper (Tfh)-like cells expressing IL21, PD-1 and Bcl-6 but lacking CXCR5 in the dermis of DLE as compared to the SLE (n=5, P=0.0060). Meanwhile, we found an increased IL-21 in the lesion of DLE, as well as in non-Tfh-like cells , which is upstream of Bcl-6. Abnormal increased IL-21 and Tfh-like cells in dermis may contribute to the formation of ectopic GCs structures and immune deposition in DLE. Our findings might provide new mechanisms for pathogenesis of DLE, as well as providing potential therapeutic targets.

Association between the ratio of aryl hydrocarbon receptor (AhR) in Th17 cells to AhR in Treg cells and SLE skin lesions

Skin lesions are typical clinical manifestations of systemic lupus erythematosus (SLE) and the biomarker for predicting SLE skin injury is not clear. We conducted a hospital-based case-control study with aim to explore the predictive value of the ratio of aryl hydrocarbon receptor (AhR) in T helper 17 (Th17) cells to AhR in regulatory T (Treg) cells (AhR ratio) in SLE skin lesions. The clinical and laboratory data were obtained from their medical records, and the AhR relative expression levels were evaluated by reverse transcription-quantitative polymerase chain reaction. Flow cytometry was applied to determine the proportion of AhR-overexpressing cells in Th17 and Treg cells. Pearson's correlation and logistic regression analyses were used to evaluate the association between AhR ratio risk of skin lesions. Results showed that the expression level of AhR in peripheral blood mononuclear cells was increased >3-fold in patients with SLE compared with that in healthy controls. Compared with control group, the percentage of AhR-overexpressing cells to Th17 cells was statistically higher in patients with SLE, whereas no significant difference was observed in the percentage of AhR-overexpressing cells to Treg cells between patients with SLE and control group. AhR ratio was also higher in SLE, and it was negatively correlated with complement 3 while positively correlated with erythrocyte sedimentation rate. In addition, compared with the low-AhR ratio group, more younger SLE patients with skin lesions, ultraviolet allergies and lower C3 levels were observed in the high-AhR ratio group, implicating that AhR ratio may be a potential biomarker for predicting SLE skin injury.

OX40L/OX40 axis impairs follicular and natural Treg function in human SLE.

Tregs are impaired in human systemic lupus erythematosus (SLE) and contribute to effector T cell activation. However, the mechanisms responsible for the Treg deficiency in SLE remain unclear. We hypothesized that the OX40L/OX40 axis is implicated in Treg and regulatory follicular helper T (Tfr) cell dysfunction in human SLE. OX40L/OX40 axis engagement on Tregs and Tfr cells not only specifically impaired their ability to regulate effector T cell proliferation, but also their ability to suppress T follicular helper (Tfh) cell-dependent B cell activation and immunoglobulin secretion. Antigen-presenting cells from patients with active SLE mediated Treg dysfunction in an OX40L-dependent manner, and OX40L-expressing cells colocalized with Foxp3+ cells in active SLE skin lesions. Engagement of the OX40L/OX40 axis resulted in Foxp3 downregulation in Tregs, and expression in SLE Tregs correlated with the proportion of circulating OX40L-expressing myeloid DCs. These data support that OX40L/OX40 signals are implicated in Treg dysfunction in human SLE. Thus, blocking the OX40L/OX40 axis appears to be a promising therapeutic strategy.

Skin inflammation induced by lupus serum was inhibited in IL-1R deficient mice

Abstract Skin lesion is the second common clinical manifestations of systemic lupus erythematosus (SLE), but its pathogenesis is not clear. IL-1 is a proinflammatory cytokine, and its role in SLE skin lesion is still unclear. We used IL-1R deficient mice and other gene deficient mice to study the role of IL-1 in the lupus serum -induced skin inflammation. We found that the severity of skin inflammation induced by lupus serum was significantly reduced in IL-1R deficient mice and caspase-1 deficient mice. IL-1R deficiency did not affect the expression of FcγRI (CD64), FcγRII (CD32) and MHC class II (CD74) induced by lupus serum. IL-1R deficiency also reduced the lipid raft clustering, and decreased expression of MCP-1 and TNFa in monocytes. Skin inflammation and keratinocyte proliferation were significantly decreased in TNFa deficient mice. Our findings indicate that IL-1 plays an important role in skin lesions of SLE. This study suggests that IL-1 is a therapeutic target in skin lesions of SLE.

Association of Anti–Acidic Ribosomal Protein P0 and Anti–Galectin 3 Antibodies With the Development of Skin Lesions in Systemic Lupus Erythematosus

The specific autoantibodies and antigens that mediate systemic lupus erythematosus (SLE)-related organ injuries remain largely unknown. This study was undertaken to investigate the antibody-mediated immune response that leads to SLE skin lesions. The study included 85 SLE patients with lupus-specific skin lesions and 31 without skin lesions. The reactivity of serum antibody with skin antigens was determined by immunoblotting using human foreskin as the substrate. Skin antigens were identified using mass spectrometry. Serum antibody was isolated by affinity purification and was injected intracutaneously into mouse skin to determine pathogenicity. Serum antibody levels were monitored by enzyme-linked immunosorbent assay. We determined that 78% of the patients with skin lesions had serum antibodies reactive with 35-kd and/or 25-kd skin antigens, which was significantly higher than the percentage of patients without skin lesions (P < 0.0001), suggesting a correlation between immune response and skin lesions. Acidic ribosomal protein P0 (RPLP0) and galectin 3 were 2 target antigens identified from 35-kd and 25-kd proteins, respectively. Purified serum anti-RPLP0 and anti-galectin 3 antibodies induced lupus-like histologic changes after intracutaneous injection. Anti-RPLP0 and anti-galectin 3 antibody levels were significantly higher in SLE patients than in healthy controls and decreased with skin recovery. Anti-galectin 3 antibody levels were not significantly higher in SLE patients than in patients with dermatomyositis or scleroderma, but strongly related to lupus cutaneous vasculitis. Additionally, levels of the 2 antibodies were positively correlated with leukopenia and C3 deficiency, and the anti-RPLP0 antibody level was also positively correlated with arthritis and SLE disease activity. Our findings indicate that the immune response mediated by serum anti-RPLP0 and anti-galectin 3 antibodies plays a key role in the pathogenesis of SLE skin lesions. These findings provide new insights into the mechanism of SLE-related organ disorders.

The association of anti-annexin1 antibodies with the occurrence of skin lesions in systemic lupus erythematosus

Anti-annexin1 antibodies are associated with the subtypes of cutaneous lupus and are elevated in systemic lupus erythematosus (SLE) patients. In this study, we investigated the correlation of this antibody with the incidence of SLE skin lesions. The presence of anti-annexin1-IgG and-IgM determined by Western blot was no different among healthy controls and SLE patients with and without skin lesions. Serum levels of anti-annexin1-IgG and -IgM measured by enzyme-linked immunosorbent assay were comparable between patients with and without skin lesions, whereas anti-annexin1-IgM was lower in SLE patients than in healthy controls. Annexin1 was abundantly detected in each epidermal layer in lupus lesional skin. Additionally, anti-annexin1-IgG was higher in SLE patients with arthritis and negatively correlated with white blood cells (WBC). Anti-annexin1-IgM was higher in patients with antinuclear antibody (ANA)-positive sera, and was positively related to hemoglobin and total serum IgM. Collectively, anti-annexin1 antibodies are not related to the incidence of skin lesions in SLE, and annexin1 abundantly distributes in epidermis in lesional skin.

Hydroxychloroquine administration for Japanese lupus erythematosus in Wakayama: A pilot study

Hydroxychloroquine (HCQ) is used as the first-line systemic treatment for severe, widespread or refractory cutaneous lupus erythematosus (CLE) in many countries. However HCQ is not an approved drug in Japan. For the establishment of HCQ therapy as the alternative treatment for CLE in Japan, we conducted a pilot study in Japanese patients with refractory CLE by administrating HCQ, and evaluated the improvements in the skin lesions using the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI). We administrated HCQ to seven CLE cases, including four systemic lupus erythematosus (SLE) cases. The skin lesions of the four cases improved dramatically, and their mean CLASI activity index decreased significantly following HCQ treatment. Arthralgia improved in all three cases with arthralgia and general malaise also improved in two of the three cases who had complained. In three cases who discontinued HCQ therapy after 16 weeks of treatment, their skin lesions and general malaise worsened soon, and after the resumption of HCQ therapy these symptoms improved again. The mean serum triglyceride and total cholesterol levels also decreased significantly at the end of this study. Our results suggest that HCQ might be effective for Japanese SLE skin lesions and CLE, and support the studies which reported that HCQ prevented clinical flare ups of SLE. An additional effect to improve lipid profiles was also observed in our Japanese cases. It is necessary to confirm that these effects are reproducible when Japanese lupus erythematosus cases are given HCQ.

IL-2, IL-5, TNF-α and IFN-γ mRNA expression in epidermal keratinocytes of systemic lupus erythematosus skin lesions

OBJECTIVE:To analyze cytokine gene expression in keratinocytes from patients with systemic lupus erythematosus (SLE).INTRODUCTION:Keratinocytes represent 95% of epidermal cells and can secrete several cytokines.METHODS:Keratinocytes were obtained by laser microdissection from 21 patients with SLE (10 discoid and 11 acute lesions) at involved and uninvolved sites. All patients were receiving a low/moderate prednisone dose and 18 were receiving chloroquine diphosphate. IL-2, IL-5, TNF-α and IFN-γ gene expression was evaluated by real-time PCR and expressed as the ratio (R) to a pool of skin samples from 12 healthy volunteers.RESULTS:Heterogeneity in cytokine gene expression was found among patients with SLE. Eighteen of 38 valid SLE samples (47%) presented overexpression (R>1) of at least one cytokine. Lesional skin samples tended to show higher cytokine expression than samples from uninvolved skin (p = 0.06). IL-5 and IFN-γ were the most commonly overexpressed cytokines. Samples with cytokine overexpression corresponded to more extensive and severe lesions. Prednisone dose did not differ between samples without cytokine overexpression (15.71±3.45 mg/day) and those with overexpressed cytokines (12.68±5.41 mg/day) (p = 0.216). Samples from all patients not receiving diphosphate chloroquine had at least one overexpressed cytokine.CONCLUSIONS:The heterogeneous keratinocyte cytokine gene expression reflects the complex immunological and inflammatory background in SLE. Patients with severe/extensive skin lesions showed a higher frequency of cytokine gene overexpression. Increased IFN-γ and IL-5 expression suggests that Th1 and Th2 cells are involved in SLE skin inflammation. The possibility that prednisone and antimalarial drugs may have contributed to low cytokine gene expression in some samples cannot be ruled out.

Melanoma Inhibitor of Apoptosis Protein (ML-IAP) Specific Cytotoxic T Lymphocytes Cross-React with an Epitope from the Auto-Antigen SS56

A large proportion of melanoma patients host a spontaneous T-cell response specifically against ML-IAP-derived peptides. In this study, we describe that some ML-IAP-specific cytotoxic T cells isolated from melanoma patients cross react with an epitope from the auto-antigen SS56. SS56 is a recently described target of autoantibody responses in Sjögren's syndrome (SS) as well as systemic lupus erythematosus (SLE). Here, we describe that SS56 is also an auto-antigen for T cells in SS and SLE. Hence, SS56-specific T cells could readily be detected in circulation and among the infiltrating cells of SLE skin lesions. SS56-specific T cells were able to lyse target cells presenting the peptide epitope on the surface. Notably, SS56-specific CD8 T cells isolated from an SS patient cross reacted with the ML-IAP epitope. This early evidence of a target for auto-reactive CTL in SS and SLE patients; it is to our knowledge previously unreported and underscores the important role of CD8 T cells in autoimmune disorders. Furthermore, the cross-reactivity against the auto-antigen SS56 and the tumor-antigen ML-IAP confirms the link between autoimmunity and anti-cancer cellular immune responses.

Role of innate immunity cytokines in systemic lupus and systemic onset arthritis

Cytokines of the innate immune system, like TNF and type I interferon (IFN-alpha/beta), have been described to be key players in autoimmunity. IFN-alpha/beta may drive many of the immune alterations described in systemic lupus erythematosus (SLE), a prototype autoimmune disease characterized by a break of tolerance to nuclear components. The recognition of the fundamental role of immature dendritic cells (DCs) in the control of peripheral tolerance led to the hypothesis that SLE may be driven through unabated DC activation. Indeed, CD14+ monocytes isolated from SLE blood, but not those from healthy individuals, act as DCs. Their activation is driven by IFN-α secreted by plasmacytoid DCs that have been shown to infiltrate SLE skin lesions. The importance of IFN-α in SLE is further shown by the presence of an IFN-α signature in the blood of all SLE patients, and by its extinction upon therapy with high-dose steroids. The excess of IFN-α may also contribute to the hypergammaglobulinemia that characterizes SLE patients, as pDCs triggered with virus induce activated B cells to differentiate into plasma cells. We have also explored the role of an innate immunity cytokine, interleukin-1 (IL-1), in the pathogenesis of systemic onset juvenile idiopathic arthritis (SOJIA), one of the major forms of chronic inflammatory arthritis in childhood. Our results indicate that this cytokine is at the center of SOJIA pathogenesis, as these patients produce an excess of IL-1 and treatment with IL-1 receptor antagonist (IL-1Ra) results in disease resolution.

The central role of dendritic cells and interferon-alpha in SLE.

Until recently, systemic lupus erythematosus has been viewed mainly as a B-cell disease resulting from altered T cell-B cell interactions. The recognition of the fundamental role of dendritic cells in the control of tolerance and immunity led to the hypothesis that systemic lupus erythematosus may be driven through unabated dendritic cell activation. This review summarizes the recently uncovered role of dendritic cell subsets and one of their products, interferon-alpha, in the pathophysiology of systemic lupus erythematosus. CD14+ monocytes isolated from the blood of patients with systemic lupus erythematosus, but not those from healthy individuals, act as dendritic cells. Their activation is driven by circulating interferon-alpha that may come from one of the dendritic cell subsets (ie, plasmacytoid dendritic cells that infiltrate systemic lupus erythematosus skin lesions). Although only a fraction of patients with active systemic lupus erythematosus show circulating interferon-alpha, blood mononuclear cells from all of them display an interferon-alpha signature. The disease model that the authors propose places interferon-alpha at the center of the immunologic abnormalities observed in systemic lupus erythematosus, and poses interferon-alpha and/or interferon-alpha-producing cells as novel targets for therapy in this disease. The authors surmise that type I interferon antagonists will bring systemic lupus erythematosus patients the relief that tumor necrosis factor antagonists brought to patients with rheumatoid arthritis.

The role of microvascular injury in the pathogenesis of cutaneous lesions of dermatomyositis

Although microvascular injury has been postulated as the pathogenetic basis of skeletal muscle injury in dermatomyositis (DM), its role in the genesis of the skin lesions, which are said to be difficult to distinguish light microscopically from systemic lupus erythematosus (SLE) and subacute lupus erythematosus (SCLE), has not been analyzed. The authors' intention was to assess the role of microvascular injury in the pathogenesis of skin lesions in DM, SLE, and SCLE. Light microscopic features of biopsies of lesional skin from 20 patients with myopathic DM and 11 with amyopathic DM were compared to eight lesional skin biopsies from eight patients with SLE and 12 lesional skin biopsies from 12 patients with SCLE. Vascular density was compared in the three groups using an inmmunohistochemical preparation with an antibody to factor VIII. In 12 biopsies from the DM group, and in 19 of 20 lupus erythematosus (LE) specimens, frozen tissue was available. An indirect immunofluorescence methodology was used to detect C 5b-9 deposition, and direct immunofluorescence studies for other immunoreactants were performed in standard fashion. Compared with LE, lesions of DM showed a greater degree of endothelial injury, vascular ectasia, and vascular fibrin deposition; there were no differences between myopathic versus amyopathic DM. C 5b-9 deposition in vessels was significantly greater in DM than in LE. The superficial vascular plexus density was reduced in lesions of DM versus LE control groups with the greatest reduction observed in myopathic DM. Epithelial injury and mucin was greatest in myopathic DM. Microvascular injury is the apparent pathophysiological basis of skin lesions in DM. Careful attention to microvascular pathology enables distinction of DM from SLE and SCLE. Indirect immunofluorescence testing using a monoclonal antibody to C 5b-9 is a valuable tool to distinguish DM from LE in biopsies of lesional skin.

The characterization of DNA antibody idiotypes—A description

The objective of this workshop was for investigators to characterize the idiotype systems they were employing to evaluate the expression of common idiotype families on the immunoglobulins and anti-DNA antibodies of patients with systemic lupus erythematosus (SLE) as well as other diseases, and in normal individuals. Twenty-four different systems were described, in which the idiotypes identified were expressed in SLE or related disorders (see Table). Each investigator was asked to provide information on the nature and source of the anti-idiotype probes employed to search for the expression of each idiotype amongst other antibodies, and the location (where known) for each idiotype on the heavy or light chain variable region, including any data on the molecular localization of idiotypic determinants. The 16/6 idiotype family and its expression in various systems was discussed by several groups. The prototype SLE peripheral-blood derived hybridoma monoclonal IgM kappa anti-DNA antibody employed to generate anti-16/6 idiotype probes showed higher binding to poly (I), poly (dT) and denatured DNA than to native DNA; it also showed binding to cell membrane antigens (platelets and lymphocytes), glycolipids extracted from the cell membrane of Mycobacteria tuberculosis, Klebsiella polysaccharide K30, and cytoskeletal structures. The expression of this idiotype was probed by a rabbit anti-16/6 polyclonal antibody, and in previous studies in SLE sera, 50% of patients with active disease expressed this idiotype on serum immunoglobulins as well as on 40% of immunoglobulins deposited in SLE skin and kidney lesions. The 16/6 Id has also been identified on paraproteins of G, M and A isotypes and in the serum of patients with mycobacterial infections during the active stages of their disease. Dr Lori Tucker (Boston) described some of the studies she is currently undertaking in Dr Schwartz's laboratory, looking at the molecular aspects of 16/6 expression. The parent 16/6 IgM~c antibody utilizes an Ig heavy chain variable region gene from the VHuI family, and the heavy chain of 16/6 is responsible for the expression of

Evaluation of ATPase-positive Langerhans' cells in skin lesions of lupus erythematosus and experimentally induced inflammations

We examined the time-dependent dynamics of epidermal Langerhans' cells (LC) in human systemic lupus erythematosus (SLE), in MRL/Mp-lpr/lpr(MRL/lpr) mice, and in various experimental cutaneous inflammations, such as the Arthus reaction, dinitrochlorobenzene allergic dermatitis, and croton oil primary irritant dermatitis, in order to clarify the pathomechanisms of lupus skin lesions. The numbers of LC in untreated SLE patients with newly developed skin lesions decreased in the central lesional sites and increased significantly in the peripheral lesional sites. In MRL/lpr mice, the number of LC increased significantly in the central lesional sites during the initial stage and increased in the peripheral lesional sites and decreased in the central lesional sites 2-4 weeks after the onset of skin lesions. In contrast, with experimental cutaneous inflammations of guinea pigs, the increase in numbers of LC in the peripheral lesional sites was not significant during the time course of the reaction. These results suggest that the increased numbers of LC during the active and early stages of skin lesions in human SLE and MRL/lpr mice are closely related to the specific spontaneous development of skin lesions, unlike the dynamics of LC in experimental cutaneous inflammations.