Chronic Discoid Lupus Research Articles

Cutaneous lupus erythematosus is associated with an increased risk of cardiac and vascular diseases: a large-scale, propensity-matched global retrospective cohort study.

Autoimmune skin diseases can expedite various systemic sequelae involving other organs. Although limited to the skin, cutaneous lupus erythematosus (CLE) was noted to be associated with thromboembolic diseases. However, small cohort sizes, partially discrepant outcomes, missing data on CLE subtypes, and incomplete risk assessment limits these findings. The Global Collaborative Network of TriNetX provides access to medical records of more than 120 million patients worldwide. We used TriNetX to elucidate the risk for cardiac and vascular diseases after diagnosis of CLE, and its subtypes chronic discoid (DLE) and subacute cutaneous lupus erythematosus (SCLE). We included 30,315 CLE, 27,427 DLE, and 1613 SCLE patients. We performed propensity-matched cohort studies determining the risk to develop cardiac and vascular diseases (ICD10CM:I00-99) following diagnosis of CLE, DLE, or SCLE. Patients with systemic lupus erythematosus were excluded. We document that CLE and its subtype DLE but less so SCLE are associated with a higher risk for various cardiac and vascular diseases. This included predominantly thromboembolic events such as pulmonary embolism, cerebral infarction, and acute myocardial infarction, but also peripheral vascular disease and pericarditis. For example, the hazard ratio of arterial embolism and thrombosis was 1.399 (confidence interval: 1.230-1.591, p<0.0001) following CLE diagnosis. The study is limited by retrospective data collection and reliance on ICD10-disease classification. CLE and its major subtype DLE are associated with an increased risk for the development of a wide range of cardiac and vascular diseases. This research was funded by Deutsche Forschungsgemeinschaft (EXC 2167, CSSL/CS01-2022) and the Excellence-Chair Program of the State of Schleswig-Holstein.

Systemic Lupus Erythematosus in Men: Brief Description of Clinical and Laboratory Findings

Background: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by the presence of nuclear autoantibodies, which can cause autoimmune complex formation and inflammation of multiple organs. It is known to affect women more frequently than men and is typically diagnosed during reproductive age, where the female-male ratio has been reported as high as 12:1. The etiology of SLE is not fully understood, but both genetic predisposition and environmental triggers are believed to be involved. Because of the multitude of presentations, manifestations, and serological abnormalities in patients with SLE, diagnosis can be challenging. Chronic discoid lupus and photosensitivity have been found in men with SLE as far as skin findings are concerned, there is less joint involvement in these patients, however, severe systemic findings predominate, such as serositis, pleurisy, central nervous system involvement with the presence of seizures. , thrombotic events and lupus nephropathy of the acute proliferative glomeruonephritis variety, serologically there is no consensus yet, nor in the specific clinical characteristics but the presence of anti-dsDNA anti-Sm antibodies and anticardiolipin antibodies is also frequently found. Therapeutic approaches predominantly involve immunomodulation and immunosuppression and are targeted to be the specific organ manifestation, with the aim of achieving low disease activity. Conclusion: We considered that although male patients with lupus are not commonly seen, the manifestations are life threatening, and timely diagnosis and treatment of the disease will lead to a better outcome for these patients.

A linked physiologically based pharmacokinetic model for hydroxychloroquine and metabolite desethylhydroxychloroquine in SARS-CoV-2(-)/(+) populations.

Hydroxychloroquine (HCQ) is Food and Drug Administration (FDA)-approved for malaria, systemic and chronic discoid lupus erythematosus, and rheumatoid arthritis. Because HCQ has a proposed multimodal mechanism of action and a well-established safety profile, it is often investigated as a repurposed therapeutic for a range of indications. There is a large degree of uncertainty in HCQ pharmacokinetic (PK) parameters which complicates dose selection when investigating its use in new disease states. Complications with HCQ dose selection emerged as multiple clinical trials investigated HCQ as a potential therapeutic in the early stages of the COVID-19 pandemic. In addition to uncertainty in baseline HCQ PK parameters, it was not clear if disease-related consequences of SARS-CoV-2 infection/COVID-19 would be expected to impact the PK of HCQ and its primary metabolite desethylhydroxychloroquine (DHCQ). To address the question whether SARS-CoV-2 infection/COVID-19 impacted HCQ and DHCQ PK, dried blood spot samples were collected from SARS-CoV-2(-)/(+) participants administered HCQ. When a previously published physiologically based pharmacokinetic (PBPK) model was used to fit the data, the variability in exposure of HCQ and DHCQ was not adequately captured and DHCQ concentrations were overestimated. Improvements to the previous PBPK model were made by incorporating the known range of blood to plasma concentration ratios (B/P) for each compound, adjusting HCQ and DHCQ distribution settings, and optimizing DHCQ clearance. The final PBPK model adequately captured the HCQ and DHCQ concentrations observed in SARS-CoV-2(-)/(+)participants, and incorporating COVID-19-associated changes in cytochrome P450 activity did not further improve model performance for the SARS-CoV-2(+) population.

Chronic Discoid Lupus: Not Fighting for “A Place in the Sun”

Chronic Discoid Lupus: Not Fighting for “A Place in the Sun”

P53 and Granzyme B may have a role in progression to malignancy in hypertrophic discoid lupus erythematosus

To the Editor: Hypertrophic discoid cutaneous lupus erythematosus (HDLE) is a rare form of chronic discoid cutaneous lupus erythematosus (DLE) characterized by epidermal hyperplasia rather than atrophy (Fig 1, A and B). Squamous cell carcinoma (SCC) can arise in scarring DLE lesions, but it occurs 10 times more often in HCLE.1 When it arises as a complication of DLE, SCC shows a higher rate of recurrence (40% vs 20%), metastatic spread (26.9% vs 6%), and progression to death (26.1% vs 1%) when compared with SCC in skin without DLE.

Current Concepts on Pathogenic Mechanisms and Histopathology in Cutaneous Lupus Erythematosus.

Cutaneous lupus erythematosus (CLE) is an interferon (IFN)-driven autoimmune disease that may be limited to the skin or can be associated with systemic lupus erythematosus (SLE). CLE occurs in several morphologic subtypes ranging from isolated, disc-shaped plaques to disseminated skin lesions. The typical histopathologic pattern of skin lesions is named interface dermatitis and characterized by a lymphocytic infiltrate and necroptotic keratinocytes at the dermo-epidermal junction. Other histopathologic patterns primarily involve the dermis or subcutis, depending on the subtype. One critical mechanism in CLE is the chronic reactivation of innate and adaptive immune pathways. An important step in this process is the recognition of endogenous nucleic acids released from dying cells by various pattern recognition receptors (PRRs), including Toll-like receptors (TLRs) and other cytosolic receptors. Crucial cells in CLE pathogenesis comprise plasmacytoid dendritic cells (pDCs) as major producers of type I IFN, T cells exerting cytotoxic effects, and B cells, previously believed to contribute via secretion of autoantibodies. However, B cells are increasingly considered to have additional functions, supported by studies finding them to occur in highest numbers in chronic discoid lupus erythematosus (CDLE), a subtype in which autoantibodies are often absent. More precise knowledge of how CLE subtypes differ pathophysiologically may allow a tailored pharmacotherapy in the future, taking into account the specific molecular signature in relation to the morphologic subtype.

Senescent Progenitor Cells in the Skin of Patients with Cutaneous Lupus Erythematosus

Senescent Progenitor Cells in the Skin of Patients with Cutaneous Lupus Erythematosus

OP0308 SENESCENT PROGENITOR CELLS IN THE SKIN OF LUPUS PATIENTS

Background:Systemic lupus erythematosus (SLE) is an autoimmune disease, which is characterized by skin lesions, amongst other symptoms. These lesions (chronic discoid lupus erythematosus (CDLE) and subacute cutaneous lupus erythematosus (SCLE)) feature lymphocytic infiltration close to basal layer of the epidermis (i.e. the location of the epidermal progenitor cells), namely the epidermal dermal junction (EDJ) area. Epidermal progenitor cells maintain the homeostasis of the skin through their proliferation and differentiation into keratinocytes. In fast turnover tissues, like the skin, a population of ‘transient amplifying cells’ (TA cells), additionally facilitates generation of enough daughter cells to maintain skin homeostasis. These cells are located in an upper layer (suprabasal layer) of the epidermis, next to the basal layer. Senescence is an irreversible and locally spreading phenomenon that induces permanent cell cycle arrest.Objectives:To evaluate expression of senescence markers p16 and p21 in the epidermal progenitor and TA niches in patients with SCLE and CDLE. This was compared to a panel of other dermatological conditions with and without infiltration close to EDJ, as disease controls, and to control skin tissue.Methods:Age-matched skin lesions from patients with SCLE (n=12), CDLE (n=8), other conditions with EDJ infiltration (e.g. lichen planus, n=22), and dermatoses without EDJ infiltration (e.g. eczema, n=27), and non-lesion control biopsies (n=3) from SLE patients were employed. p16 and p21 expression in the progenitor niche (basal layer) and TA cell niche (suprabasal layer), and the whole epidermis of skin lesions biopsies were examined by immunohistochemistry.Results:In healthy skin biopsies, 0 ± 0 SEM p16+ cells/mm2 in the progenitor niche and 5 ± 4 SEM p21+ cells/mm2 in TA niche were observed. In skin lesions from patients with CDLE and SCLE, significantly more p16+ cells in the progenitor cell niche (45 ± 14 SEM/mm2) and p21+ cells (182 ± 38 SEM/mm2) in TA niches were detected, compared to control biopsies (p &lt; 0.05), and compared to those dermatoses without EDJ infiltration (p16+ 11 ± 3 SEM/mm2, p21+ 86 ± 28 SEM/mm2, p &lt; 0.05, Figure 1). p16 and p21 expression in CDLE and SCLE lesions did not significantly differ from other dermatoses with EDJ infiltration (p&gt;0.05). Across all dermatoses analyzed, the number of p16+ cells was significantly correlated with the number of p21+ cells, both in the progenitor niche (r=0.45, p&lt;0.0001) and TA niche (r=0.47, p&lt;0.0001). p16+ cells however were more frequently found in the progenitor cell niche, and p21+ cells conversely in the TA cell niche (p&lt;0.0001).Figure 1.Increased p16+ and p21+ cells in the progenitor and TA niches in dermatoses with EDJ infiltration. A. Graphic illustration for the progenitor cell niche (the basal layer), the transient amplifying (TA, the supra-basal layer) cell niche, and the further differentiated area. B-D. Representative staining of p16 (blue) and epidermal growth factor receptor (EGFR, brown, an epithelial cell marker) in dermatoses with (CDLE) and without (PMLE) epidermal-dermal junction (EDJ) infiltration groups. Black arrowheads point to p16+ progenitor epidermal cells. E-G. Representative staining of p21 (blue) and EGFR (brown) in dermatoses with (CDLE) and without (PMLE) EDJ infiltration groups. Hollow arrowheads point to p21+ TA epidermal cells. The dashed line indicates the EDJ. CDLE: chronic discoid lupus erythematosus, PMLE: polymorphous light eruption.Conclusion:In CDLE and SCLE, cutaneous manifestations of SLE, more progenitor and TA cells expressing markers of senescence were detected. This was in common with other dermatological conditions where lymphocytic infiltration is in close proximity to the progenitor and TA cell niche, namely in the EDJ. Increased senescence might infer the collapse of homeostasis in target (local) epidermis, which may influence tissue repair in the lesion. Elimination of senescent cells may therefore represent a viable therapeutic option to encourage timely and complete wound healing, in skin lesions of CDLE and SCLE patients.Acknowledgements:This research was funded by a China Scholarship Council grant (201606220074), Dutch Arthritis Foundation Translational Research Grant (T015-052) and a Dutch Arthritis Foundation Long Term Project Grant (LLP-29).Disclosure of Interests:None declared.

NKG2D and its ligands as cytotoxic factors in cutaneous lupus erythematosus.

Cutaneous lupus erythematosus (CLE) is an autoimmune skin disorder that is characterized by an anti-epidermal lymphocytic infiltrate invading the dermo-epidermal junction, causing an interface dermatitis (ID). Pathogenesis of CLE has been linked to activation of innate immunity. NKG2D is an innate immune receptor on NK cells and distinct T-cell populations. The NKG2D ligands MHC class I polypeptide-related sequence A and B (MICA, MICB) have been associated to CLE susceptibility. Our gene microarray analyses of chronic discoid lupus erythematosus (CDLE) skin lesions, separated in epidermal, junctional and dermal skin areas via laser microdissection, revealed a high expression of NKG2D in the lymphocytic infiltrate and led us to further investigate the role of NKG2D in CLE. Pathway analyses showed a strong "interferon (IFN) signature" and vast activation of innate immune response pathways (TLR, RIG-I, cytosolic DNA sensing, JAK/STAT) in CDLE, that expressed the high NKG2D signal. Immunohistochemistry (IHC) confirmed the presence of NKG2D and its ligand MICB in CDLE and subacute cutaneous lupus erythematosus (SCLE) lesions. Finally, HaCaT cells were stimulated with nucleic acids and extracted RNA was sequenced with Illumina HiSeq and showed that stressed keratinocytes express typical NKG2D ligands MICA/B and ULBP2. This study provides first evidence that NKG2D is present in CDLE and SCLE skin lesions and could be relevant for cytotoxicity in IFN-driven skin lesions with upregulated innate immune response pathways present in CLE. It could furthermore play a role in CLE inflammation promoted by keratinocytes under cell stress.

The Koebner phenomenon on tattoos and piercings in a patient with cutaneous lupus: a case report and review of the literature

The Koebner phenomenon is associated with cutaneous lupus erythematosus (CLE). A 20-year-old woman with a 10-year history of systemic lupus, treated with hydroxychloroquine and methotrexate, presented with features of chronic discoid lupus erythematosus (DLE) on the scalp, at the site of ear piercings, and on the temporal bone at the site of trauma from her jewelry. She also had subacute CLE (SCLE) lesions on old black tattoos. Histology and direct immunofluorescence confirmed CLE. We reviewed 13 cases of Koebner phenomenon on tattoos in patients with CLE (seven men, median age: 31.5 years) and none after piercings. Lesions developed within 1 week to 16 years after tattooing. Lesions may be isolated, precede, or be associated with other CLE lesions. They can appear secondarily on the tattoo. There is no specific color affinity, but cases have shifted from red to black, possibly when mercury was withdrawn from red inks. CLE on tattoos is a rare phenomenon that more often presents with DLE features than SCLE. Patients should be warned of the potential risk of developing lesions on tattoos. Immunosuppressive treatment needs to be taken into account if a patient wishes to get a tattoo. However, tattooing is not associated with severe complications.

Two Unusual Cases of Discoid Lupus Erythematosus Associated With Xanthomatized Macrophages

We present 2 patients with chronic discoid lupus erythematosus (LE) associated with xanthomatized macrophages on light microscopic findings. Skin biopsies revealed hyperkeratotic and atrophic epidermis, vacuolar degeneration of the dermal-epidermal junction, thickened basement membrane, follicular plugging, and perivascular and perifollicular lymphohistiocytic infiltrate. Notably, large collections of lipid-laden histiocytes were observed within the subjacent dermis. The patients denied history of intralesional steroid treatment. The patients did not demonstrate any clinical or laboratory signs of hyperlipidemia, cholestasis, and diabetes mellitus and insipidus. Accumulation of lipid-laden foam cells in cutaneous LE is a rare phenomenon that has been reported in discoid LE and lupus panniculitis, each only once in the literature. It has also been described within lesions of various other dermatoses in patients without lipid, hepatic, or endocrine abnormalities. Its mechanism remains unclear, but it has been hypothesized that intracellular lipids released from degenerating cells contribute to lipidization of mononuclear scavengers. Xanthomatous infiltration in cutaneous LE is an unusual feature, and its presence may not necessarily signify an underlying metabolic disorder.

Linear lesions on the arm of a child: a diagnostic challenge

There are a number of conditions that follow the lines of Blaschko. Linear discoid lupus erythematosus is a rare variant of chronic lupus erythematosus with less than 20 cases reported in children. It can be misdiagnosed as lichen striatus or linear morphea. We describe a 15-year-old boy with a confirmed histologic diagnosis of linear chronic discoid lupus erythematosus following the lines of Blaschko, with no signs of systemic involvement.

Plucked hair follicles from patients with chronic discoid lupus erythematosus show a disease-specific molecular signature

ObjectiveWhen faced with clinical symptoms of scarring alopecia—the standard diagnostic pathway involves a scalp biopsy which is an invasive and expensive procedure. This project aimed to assess if plucked hair...

Chronic Discoid Lupus: An uncommon cause of nail atrophy.

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Squamous Cell Carcinoma of the Lower Lip Arising in Discoid Lupus Lesion - A Case Report

Introduction: Rare examples from the literature report a possible degeneration of mucosal lesions of L.E.C. We report a case of squamous cell carcinoma grafted on a lesion of the lower lip in a patient followed for L.E.C. at the ENT and Maxillo-facial department of Mohamed VI University Hospital of Oujda.Case report: A 47-year-old man, with a notion of photosensitivity, presents atrophic erythematous-violet plaques in the photo-exposed zones evolving for 20 years, evoking chronic discoid lupus cutaneous without any clinical, biological or radiological sign of systematization. The patient had a painful lower ulcer-budding process that had been evolving for 2 years, with suspected bilateral cervical lymphadenopathy. The biopsy revealed a well-differentiated infiltrating squamous cell carcinoma. Surgical excision oncology is then performed with a labial plasty and an obviously bilateral lymph node. Conclusion: The risk of degeneration of skin lesions of lupus discoid is minimal and rare, although monitoring of lupus scars remains essential, especially in the context where exposure to ultraviolet radiation is added as a predisposing factor for possible malignant transformation, surgical treatment is required at the appearance of suspicious lesions confirmed histologically.

Toxic Epidermal Necrolysis vs Lupus Flare?

SESSION TITLE: Critical Care 2 SESSION TYPE: Affiliate Case Report Poster PRESENTED ON: Tuesday, October 31, 2017 at 01:30 PM - 02:30 PM INTRODUCTION: Toxic epidermal necrolysis (TEN) and Stevens Johnson syndrome (SJS) are severe mucocutaneous reactions characterized by extensive necrosis and detachment of epidermis. Systemic lupus erythematosus (SLE) patients are at increased risk of SJS/TEN. Here we discuss a patient with SLE who developed TEN. CASE PRESENTATION: A 45 year old female with discoid and systemic lupus erythematosus presented to dermatology with bullous skin lesions 2 days after starting gabapentin, naproxen, and duloxetine. Despite stopping her new medications, she developed a facial rash which spread to her trunk and extremities, affecting 30% body surface area. She had denuded oral mucosa and conjunctival hyperemia with no photosensitivity or eosinophilia. Complements were normal. Wedge biopsy showed acute on chronic vacuolar interface dermatitis with epidermal ulceration and partial to full-thickness epidermal necrosis, suggestive of chronic discoid lupus with superimposed bullous eruption. The patient was admitted to the ICU and treated with intravenous immunoglobulin for three days. Home medications were held. Supportive care included intravenous hydration, reverse isolation in heated environment, specialized wound care, oral and eye care. Methicillin resistant staphylococcus aureus bacteremia was treated. The patient clinically improved and was in reepithelialization phase at time of discharge. DISCUSSION: The incidence of TEN is 0.4-1.2% per million. In patients with SJS/TEN, the prevalence of SLE is estimated to be 1.2% (compared to 0.02-0.05% in the general population). It is unclear if the predisposition for TEN in SLE patients is because of the underlying inflammatory state or because of medications SLE patients often require, such as NSAIDs. Differentiating SLE from TEN is complicated by clinical and histologic similarities. Pathology often demonstrates subepidermal vacuoles, necrotic keratinocytes, and confluent epidermal necrosis, which is found in SLE and TEN. Bullous eruptions and erosive mucosal involvement are typical features in TEN, but can also be found in SLE. This patient developed skin and mucosal lesions after starting new medications and had improvement without steroids, which makes active SLE less likely. Normal complement and serology also supports the clinical diagnosis of TEN over active SLE. CONCLUSIONS: Mortality in patients with SJS and TEN exceeds 10 and 30% respectively. Because the management of active SLE lesions and TEN differ greatly, early recognition of TEN can be life saving. High index of suspicion, early biopsy, and serology can be helpful in differentiating such cases. Reference #1: M. Ziemer, et al, “Stevens-Johnson syndrome and toxic epidermal necrolysis in patients with lupus erythematosus: a descriptive study of 17 cases from a national registry and review of the literature,” Brit J Dermatol 2012; 166 (3), 575-600. Reference #2: Ranario JS, et al. Bullous lesions in a patient with systemic lupus erythematosus. J Clin Aesthet Dermatol 2014; 7:44-49 DISCLOSURE: The following authors have nothing to disclose: Gauri Behari, Sukhdeep Malhi, Bradley Tymchuk, Ronnie Self II, Suman Lata, Ibrahim El-Abbassi No Product/Research Disclosure Information

Podoplanin Expression Is Correlated With the Progression of Chronic Discoid Lupus Erythematosus to Lip Squamous Cell Carcinoma.

Chronic lip discoid lupus erythematosus (DLE) is a potentially malignant disorder that can develop into lip squamous cell carcinoma (LSCC). Podoplanin is a specific marker for lymphatic endothelial cells and plays a role in cancer progression. The objective of this study was to determine the immunoexpression of podoplanin in samples of patients with DLE and its correlation with the risk of progression to LSCC. In a retrospective study, podoplanin expression was determined using immunohistochemistry in samples from 52 patients with DLE, including 44 patients with untransformed DLE and 8 patients with malignant transformed DLE. Ten samples of normal oral mucosa and 10 samples of LSCC were used as normal and cancer controls, respectively. The results showed that podoplanin expression was observed in 12 of 44 (27.3%) patients with untransformed DLE and in 7 of 8 (87.5%) patients with transformed DLE (P = .002). Podoplanin was not expressed in normal oral mucosa, but it was overexpressed in all of the 10 patients with LSCC. Regression analysis revealed that podoplanin expression was significantly associated with an 18.67-fold increase in the risk of malignant progression (95% confidence interval = 2.07-168.10; P = .009). In summary, podoplanin expression is significantly associated with malignant transformation of DLE into LSCC. Thus, podoplanin expression may identify a subgroup with a high risk of malignant progression of DLE.

Unusual Clinical Manifestations of Chronic Discoid Lupus Erythematosus

Abstract A 22-year-old woman with a 3-year history of discoid lupus erythematosus presented with two circumscribed patches of non-scarring alopecia, clinically simulating alopecia areata. Histopathological analysis of scalp lesions revealed discoid lupus erythematosus. Based on the clinical history, physical examination, and histological and immunological findings, we distinguished our case from a true combination of alopecia areata and typical chronic discoid lupus erythematosus.

T regulatory cells and related immunoregulatory factors in polymorphic light eruption following ultraviolet A1 challenge

Polymorphic light eruption (PLE) is considered to be an autoimmune-mediated skin condition in which the normal ultraviolet (UV)-induced local immunosuppression appears to be absent, leading to recognition of photoinduced autoantigens and subsequent inflammation. To investigate T regulatory cells (Tregs) and related immunoregulatory factors in PLE lesions and controls. Skin biopsies were performed in 13 patients with UVA1-challenged PLE, 12 female patients with chronic discoid lupus erythematosus (CDLE) and 11 healthy controls who had exposure to UVA1. Immunohistochemistry and four-colour immunofluorescence studies were performed. Patients with CDLE and UVA1-exposed controls showed significantly decreased epidermal immunoreactivity for CD1a compared with patients with PLE (P = 0·0001). Four-colour immunofluorescence revealed a median percentage of CD4+CD25+FOXP3+ Tregs of 7·6% (range 3·7-13·6%) in PLE, a median of 11·7% (range 9·5-13·9%) in CDLE and a median of 3·4% (range 0-6·8%) in controls. Compared with UVA1-exposed controls, PLE and CDLE lesions showed significantly decreased transforming growth factor (TGF)-β1 immunoreactivity in the epidermis (P = 0·0003). In PLE lesions, we observed significantly decreased interleukin (IL)-10 expression compared with CDLE (P = 0·022). In the dermis, receptor activator of nuclear factor-κB ligand (RANKL) expression was increased in UVA1-exposed controls compared with PLE and CDLE (P = 0·018). Similar to CDLE lesions, UVA1-challenged PLE lesions display an altered immunoregulatory network, as indicated by decreased epidermal or dermal expression of TGF-β1, IL-10 and RANKL, and a relatively low number of Tregs, particularly when compared with other inflammatory skin conditions reported in the literature.

Association of HLA-DRB1*15 and HLA-DQB1* 06 with SLE in Saudis

BACKGROUND AND OBJECTIVESSystemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by humoral autoimmunity. The etiology of SLE is thought to be multifactorial including environmental, hormonal, and genetic factors. The human leukocyte antigen (HLA) has extensively been associated with the susceptibility to SLE; however, the association is heterogeneous among different ethnic groups. The aim of this study was to determine the association of HLA-A, HLA-B, HLA-DRB1, and HLA-DQB1 with SLE susceptibility in the Saudi population.DESIGN AND SETTINGSA total of 86 consecutive SLE patients attending the rheumatology clinic at King Abdulaziz Medical City, Riyadh, were recruited for this study.METHODSHLA types were determined by the polymerase chain reaction sequence-specific oligonucleotide (PCR-SSP) method in 86 patients and 356 control subjects.RESULTSThe following HLA alleles were found to be positively associated with SLE: HLA-A*29 (OR=2.70; 95% CI=1.03–7.08; P=.0035), HLA-B*51 (OR=1.81; 95% CI=1.17–2.79; P=.0066), HLA-DRB1*15 (OR=1.45; 95% CI=0.98–2.29; P=.063), and HLA-DQB1*06 (OR=1.67; 95% CI=1.19–2.36; P=.0032), whereas HLA-DRB1*16 was negatively associated with the disease (OR=0.18; 95% CI=0.02–1.3; P=.055). HLA-DRB1*15 haplotypes were significantly associated with SLE (OR=2.01, 95% CI=1.20–3.68, P=.008); this was mainly due to the HLA-DRB1* 15-DQB1*06 association.CONCLUSIONSOur data suggest an association between MHC class I and class II (HLA-A*29, HLA-B*51, HLA-DRB1*15, and HLA-DQB1*06) and susceptibility to SLE in the Saudi population. HLA-DRB1*15-DQB1*06 haplotype showed the highest risk factor for the disease that is similar to what was seen in the African American patients, suggesting shared susceptibility genetic factors among these ethnic groups.