Correction to: Homocysteine levels are independently associated with damage accrual in systemic lupus erythematosus patients from a Latin-American cohort

Clinical Rheumatology - The affiliations of Manuel F. Ugarte-Gil, one of the author of the above article has a discrepancy between the online version of the publisher’s internet portal (...     

Male systemic lupus erythematosus in a Latin-American inception cohort of 1214 patients

The objective of the study was to evaluate the influence of the male gender in the clinical presentation and outcome of systemic lupus erythematosus in a prospective inception cohort of Latin-American patients. Of the 1214 SLE patients included in the GLADEL cohort, 123 were male. Demographic characteristics as well as clinical manifestations, laboratory profile, activity and damage scores were evaluated at onset and during the course of the disease and compared with female patients. The median age at onset of the male patients was 27 and that at diagnosis 29.2 years. Delay to diagnosis was shorter in males (134 versus 185 days, P = 0.01). At onset, men more frequently showed fever (42.3 versus 27.0%, P = 0.001) and weight loss (23.6 versus 11.8%, P = 0.001). During disease course the incident of symptoms was: fever, 67.8 versus 55.6%, P = 0.012; weight loss, 47.2 versus 24.3%, P = 0.001; arterial hypertension, 37.4 versus 25.8%, P = 0.007; renal disease (persistent proteinuria and/or cellular casts), 58.5 versus 44.6%, P = 0.004); and hemolytic anemia, 19.5 versus 10.9%, P = 0.008. The laboratory results showed that: men more frequently had IgG anticardiolipin antibodies (68.2 versus 49%, P = 0.02) and low C3 (61.3 versus 48.1%, P = 0.03); 5/123 men died (4%) compared with 29/1091 women (2.7%). In conclusion, 10% of GLADEL's cohort patients were male. They showed a distinctive profile with shorter delay to diagnosis, higher incidence of fever, weight loss, arterial hypertension, renal disease, hemolytic anemia, IgG anticardiolipin antibodies and low C3. Although not statistically significant, mortality was higher in men.     

Disease activity and damage are not associated with increased levels of fatigue in systemic lupus erythematosus patients from a multiethnic cohort: LXVII

Objective

To determine the factors associated with increased levels of fatigue over the course of the disease in systemic lupus erythematosus (SLE) patients from LUpus in MInorities: NAture versus nurture, a longitudinal multiethnic cohort.

Methods

Patients with SLE (according to the American College of Rheumatology revised and updated criteria) age ≥16 years with a disease duration ≤5 years at entry into the cohort, and of Hispanic (Texan or Puerto Rican), African American, or Caucasian ethnicity were studied. The association between socioeconomic/demographic characteristics, health behaviors, behavioral and psychological, functional and clinical characteristics, and fatigue was examined using generalized estimating equations to account for the longitudinal nature of the data.

Results

A total of 515 patients (～91% female) contributed 2,609 visits to these analyses. Of these patients, 93 (18.1%) were Texan‐Hispanic, 101 (19.6%) were Puerto Rican‐Hispanic, 169 (32.8%) were African Americans, and 152 (29.5%) were Caucasian. The mean ± SD patient age and followup time were 37.2 ± 12.6 years and 4.7 ± 3.2 years, respectively. Variables associated with increased levels of fatigue in the multivariable analyses were Caucasian ethnicity, the presence of constitutional symptoms (fever, weight loss), and higher levels of pain, abnormal illness‐related behaviors, and helplessness (P values between 0.0018 and <0.0001).

Conclusion

The presence of pain, abnormal illness‐related behaviors, helplessness, and constitutional manifestations were associated with increased levels of fatigue. However, SLE‐specific measures, such as disease activity and damage, were not. Interventions aimed at decreasing fatigue need to take into account these findings.     

Homocysteine levels and disease duration independently correlate with coronary artery calcification in patients with systemic lupus erythematosus

OBJECTIVE: To compare the incidence and extent of coronary artery calcification (CAC) as measured by electron beam computed tomography (EBCT) in patients with systemic lupus erythematosus (SLE) and controls, and to identify variables associated with CAC in patients with SLE. METHODS: Female patients with SLE and matched controls were recruited; EBCT of the coronary arteries was performed, and laboratory values (including the homocysteine concentration, the lipid level, the high-sensitivity C-reactive protein [hsCRP] concentration, the glomerular filtration rate [GFR], and the level of soluble CD154 [sCD154]) were determined. For patients, the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index and the SLE Disease Activity Index scores were recorded. Tests of association between the CAC score and the above-mentioned variables were performed. RESULTS: The incidence of CAC was higher in patients with SLE than in controls (P = 0.009), and patients had a higher mean raw CAC (rCAC) score (87.9 versus 9.6 in controls; P = 0.02). In particular, more CAC-positive patients than CAC-positive controls had rCAC scores above the 75th percentile (P = 0.003). Among both patients and controls, those with CAC were approximately 10 years older than those without CAC. In addition to age, a significant determinant of positive CAC status in both groups was the number of cardiovascular risk factors. In patients with SLE, CAC was associated with a higher homocysteine concentration, a lower GFR, and longer disease duration. In controls, the total cholesterol level correlated positively with CAC. When multivariate logistic regression methods were applied to candidate explanatory variables, homocysteine concentration, age, and disease duration (but not the levels of sCD154 or hsCRP) contributed significantly to CAC status. The methylenetetrahydrofolate reductase C677T genotype was not a predictor of hyperhomocysteinemia or CAC status. CONCLUSION: Among patients with SLE, the homocysteine concentration, the GFR, age, and disease duration were associated with CAC. CAC occurred more frequently and was more extensive in patients with SLE than in controls, suggesting that EBCT could be used to detect premature atherosclerosis in the former group. An elevated homocysteine concentration might identify patients with SLE who are likely to have premature atherosclerosis and who would benefit from evaluation of CAC by EBCT.     

Accelerated damage accrual among men with systemic lupus erythematosus: XLIV. Results from a multiethnic US cohort

OBJECTIVE: To determine the impact of the patient's sex on the manifestations and outcome of systemic lupus erythematosus (SLE). METHODS: We studied SLE patients who were ages 16 years or older and had a disease duration of < or =5 years at the time of enrollment in the LUpus in MInorities, NAture versus nurture cohort, a multiethnic cohort consisting of Hispanic, African American, and Caucasian patients. Socioeconomic/demographic, clinical, and serologic features, as well as disease activity (by the Systemic Lupus Activity Measure, Revised) and damage accrual (by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index) were compared between male and female patient groups. Multivariable analyses using male sex and damage accrual as dependent variables were then performed. RESULTS: Sixty-three male SLE patients (10.2%) from all ethnic groups were included. The mean ages of the male and female patients were comparable. Factors that were either more frequent or tended to be more frequent among male SLE patients were Caucasian ethnicity, smoking, alcohol use, lupus anticoagulant (LAC) positivity, and renal involvement, whereas musculoskeletal involvement was less common. American College of Rheumatology criteria accrual time and disease duration were shorter in the male patients; damage was more common and of higher magnitude in this group. LAC positivity, shorter disease duration, and higher early damage scores were independently associated with male SLE. Male sex was a strong predictor of baseline damage, measured as a categorical variable (t-test = 2.357, beta-standardized coefficient 0.113; P = 0.019) or a continuous variable (hazard ratio 3.179 [95% confidence interval 1.999-5.056]; P < 0.001). Male sex was also positively associated with the development of damage over most of the course of the disease. CONCLUSION: Poorer long-term prognosis among men with SLE appears to be decisively determined by their accelerated development of damage, particularly early in the course of the disease.     

Association of discoid lupus erythematosus with clinical manifestations and damage accrual in a multiethnic lupus cohort

Objective

To determine the clinical manifestations and disease damage associated with discoid rash in a large multiethnic systemic lupus erythematosus (SLE) cohort.

Methods

SLE patients (per American College of Rheumatology [ACR] criteria) ages ≥16 years with a disease duration of ≤10 years at enrollment and defined ethnicity (African American, Hispanic, or white) from a longitudinal cohort were studied. Socioeconomic–demographic features, clinical manifestations, and disease damage (per the Systemic Lupus International Collaborating Clinics/ACR Damage Index) were determined. The association of discoid lupus erythematosus (DLE) with clinical manifestations and disease damage was examined using multivariable logistic regression.

Results

A total of 2,228 SLE patients were studied. The mean ± SD age at diagnosis was 34.3 ± 12.8 years and the mean ± SD disease duration was 7.9 ± 6.0 years; 91.8% were women. DLE was observed in 393 patients with SLE (17.6%). In the multivariable analysis, patients with DLE were more likely to be smokers and of African American ethnicity and to have malar rash, photosensitivity, oral ulcers, leukopenia, and vasculitis. DLE patients were less likely to be of Hispanic (from Texas) ethnicity and to have arthritis, end‐stage renal disease, and antinuclear, anti–double‐stranded DNA, and antiphospholipid antibodies. Patients with DLE had more damage accrual, particularly chronic seizures, scarring alopecia, scarring of the skin, and skin ulcers.

Conclusion

In this cohort of SLE patients, DLE was associated with several clinical features, including serious manifestations such as vasculitis and chronic seizures.     

Damage accrual in southern Chinese patients with systemic lupus erythematosus

OBJECTIVE: To study the predictive factors of damage accrual in a large cohort of southern Chinese patients with systemic lupus erythematosus (SLE). METHODS: A cohort of consecutive Chinese patients with SLE was recruited in 1998 and prospectively followed for 3 years. Demographic data, disease manifestations and activity, medication use, and damage scores were recorded. Organ damage was assessed using the SLE International Collaborating Clinics Damage Index (SDI), which was scored at study entry and then annually. Disease flares and new damage were recorded during followup visits. Predictive factors of new damage were studied by statistical analysis. RESULTS: The cohort consisted of 242 consecutive patients with SLE (221 women, 21 men; F:M = 10.5:1). All fulfilled at least 4 American College of Rheumatology criteria for the classification of SLE. At entry, mean age was 35.7 +/- 10.7 years and mean disease duration was 75.3 +/- 79 months. Ninety (38%) patients had damage. The mean SDI score at year 0 was 0.76 +/- 1.3 (range 0-8), and this increased significantly to 1.33 +/- 1.7 (range 0-9) at year 3 (p < 0.001). The most frequent organ damage at entry was musculoskeletal (26.5%), followed by damage in central nervous system (18.4%), renal (15.1%), and cardiovascular (12.4%) systems. The increase in SDI scores over the 3 year period was primarily caused by the increase in renal, musculoskeletal, and gonadal damage. Twelve patients died. Multiple regression revealed that the number of major disease flares and the use of cyclophosphamide were independent factors predictive of damage accrual. An increase in SDI scores was associated with mortality risk (OR 1.47 per 1 point, 95% CI 1.03-2.11, p = 0.04). CONCLUSION: The damage scores of our SLE cohort increased significantly over 3 years. Severe disease flares and the use of cyclophosphamide predicted new damage. Increase in damage was associated with mortality risk. Judicious use of immunosuppressive agents to achieve prompt control of disease activity was essential in minimizing damage and improving survival of our patients with SLE.     

SLICC/ACR damage index independently associated with left ventricular diastolic dysfunction in patients with systemic lupus erythematosus

Left ventricular (LV) diastolic dysfunction has been reported in both active and inactive systemic lupus erythematosus (SLE) patients without clinical evidence of cardiovascular disease. However, the relationship between the long-term inflammatory burden reflected by the SLICC/ACR damage index and LV diastolic function has not been studied. Eighty-two SLE patients and 82 controls matched for age, sex, body mass index, blood pressure and heart rate underwent echocardiography with tissue Doppler imaging (TDI). LV diastolic function was estimated by the myocardial early diastolic velocity (E') at the lateral annulus. There were 51 patients (62.2%) with nephritis, 23 patients (28.0%) with hypertension, 21 patients (25.6%) with vasculitis, 16 patients (19.5%) with pulmonary hypertension, 4 patients (4.9%) with cerebrovascular disease and 2 patients (2.4%) with diabetes mellitus. Sixty-two patients (75.6%) were taking prednisone and 35 patients (42.7%) used a immunosuppressant. Forty-five patients (54.8%) had active disease and suffered from disease-related end-organ damage. Patients with SLICC/ACR damage index ≥1 had more evidence of LV diastolic dysfunction with lower lateral annulus E' (9.6?±?3.4 vs 12.9?±?3.5?cm/s, p?相似文献   

Greater accrual damage in late-onset systemic lupus erythematosus: a long-term follow-up study

The main objective of this study was to evaluate the clinical differences and the pattern and extent of organ damage in late-onset systemic lupus erythematosus (SLE). A nested case-control study was performed from patients with SLE followed in the Rheumatology Unit of the State University of Campinas between 1974 and 2005. Patients who developed SLE after the age of 49 were considered late-onset SLE. SLE patients with age <49 years, matched for sex, ethnicity, disease duration and organ damage at study entry were randomly chosen to compose the control group. Baseline and cumulative clinical manifestations, laboratory data, SLE disease activity index (SLEDAI), Systemic Lupus International Collaborating Clinics/American College of Rheumatology-damage index (SDI) and mortality were compared between groups. At diagnosis and follow-up, late-onset group had lower SLEDAI scores when compared with younger age onset. Clinically, they presented less frequently arthritis (P = 0.0002) and malar rash (P = 0.02) and more frequently Raynaud's phenomenon (P = 0.002) and arterial hypertension (P = 0.02) when compared with young onset at diagnosis. Late-onset SLE received lower total corticosteroid dose (P < 0.001) and less frequently cyclophosphamide (P = 0.01). During the study period, late-onset SLE had always lower SLEDAI scores (P = 0.001). At study endpoint, late-onset SLE patients had significantly higher SDI scores (P = 0.001) and a higher mortality rate when compared with younger onset group (P < 0.01). In conclusion, late-onset SLE is milder on presentation and during course of disease, but patients have more organ damage and a higher rate of mortality than young onset SLE. Patients with late onset should be followed with close monitoring and early identification of complications is mandatory in this subgroup of patients with SLE.     

A comparison of damage accrual across different calendar periods in systemic lupus erythematosus patients

Therapeutic approaches in systemic lupus erythematosus (SLE) have evolved over the last few decades, but their impact on prevention of organ damage is unknown. The objective of this study was to compare new cumulative damage in SLE patients across different calendar periods. Patients from a large SLE cohort were divided into two subcohorts; the first diagnosed and followed between 1978 and 1988 (cohort #1, n=100) and the second between 1989 and 1999 (cohort #2, n=51). Initial Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR DI) scores, and changes in scores over the observation intervals, were compared for the two groups. Logistic regression estimated adjusted odds ratios (OR) comparing damage accrual between the two cohorts. Medication exposures were noted. Baseline characteristics were similar between the two groups. At first assessment, the adjusted OR for a SLICC/ACR DI score > or =1 was 1.79 (95% CI 0.82, 3.88) for cohort #1 versus cohort #2. At the end of the observation interval, the adjusted OR for a SLICC/ACR DI score > or =1 was 1.22 (0.58, 2.55) for cohort #1 versus cohort #2. The adjusted OR for accruing damage over the observation interval in cohort #1 versus cohort #2 was 0.94 (0.39, 2.44). Increased medication exposure was evident for cohort #2 compared to cohort #1. Despite increased therapeutic measures used for patients in more recent periods, our data do not establish a clear difference in damage accrual. This emphasizes the need for strategies to effectively treat lupus-specific manifestations, while minimizing side effects and comorbidities.     

Decreases in anti-double-stranded DNA levels are associated with concurrent flares in patients with systemic lupus erythematosus

OBJECTIVE: To determine the degree to which changes in anti-double-stranded DNA (anti-dsDNA), as determined by Crithidia and enzyme-linked immunosorbent assays (ELISAs), precede or coincide with changes in systemic lupus erythematosus (SLE) activity, as measured by 5 clinical indices, the physician's global assessment (PGA), modified SLE Disease Activity Index (M-SLEDAI), modified Lupus Activity Index (M-LAI), Systemic Lupus Activity Measure (SLAM), and the modified British Isles Lupus Assessment Group (M-BILAG). METHODS: Disease activity and anti-dsDNA were measured monthly in 53 SLE patients who were followed up for 1 year. Lupus flare was defined as an increase in PGA of > or = 1.0, M-SLEDAI > or = 3, M-LAI > or = 0.1, SLAM > or = 3, and M-BILAG > or = 4 within a 1-month period. Flare rates were calculated for groups, which were defined by "previous" (1 month prior to the flare) or "concurrent" (at the time of the flare) changes in anti-dsDNA. Logistic regression models were used to determine the significance of the association between recent changes in anti-dsDNA and flare, controlling for the prednisone dosage. RESULTS: Flares occurred at 12% of visits, based on the PGA measure of disease activity. Using the other indices, flare rates were 19% (M-SLEDAI), 25% (M-LAI), 13% (SLAM), and 12% (M-BILAG). A concurrent decrease in anti-dsDNA (ELISA) was associated with significantly higher flare rates based on PGA (18 of 84, 21%; P = 0.0014), M-SLEDAI (27 of 89, 30%; P = 0.0019), M-LAI (37 of 89, 42%; P = 0.0001), and M-BILAG (19 of 89, 21%; P = 0.0264) scores. Flare rates were also significantly higher after a previous increase in anti-dsDNA (ELISA) based on M-SLEDAI (26 of 93, 30%; P = 0.0022) and M-LAI (34 of 93, 37%; P = 0.0117) scores. Flare rates tended to be lowest when there was a concurrent increase in anti-dsDNA (ELISA). Analysis of specific organ systems showed that a concurrent decrease in anti-dsDNA (ELISA) was significantly associated with increases in renal disease activity. Similar results were obtained using the Crithidia assay. CONCLUSION: A previous increase in anti-dsDNA levels occurred before SLE flares, as measured by the M-SLEDAI and M-LAI only. However, during lupus flares, including the subset of renal flares, anti-dsDNA levels frequently decreased. We hypothesize that this decrease in anti-dsDNA represents deposition in tissue at the time of flare.     

Predictors of post-partum damage accrual in systemic lupus erythematosus: data from LUMINA, a multiethnic US cohort (XXXVIII)

OBJECTIVE: To determine the impact of pregnancy on systemic lupus erythematosus (SLE) outcome. METHODS: SLE patients, age >or=16 yrs, disease duration 相似文献   

Serum free prolactin concentrations in patients with systemic lupus erythematosus are associated with lupus activity

OBJECTIVE: To determine in patients with systemic lupus erythematosus (SLE) the relationships among serum total and free prolactin (PRL) levels, isoforms of PRL and lupus activity. METHODS: In a cross-sectional study, 259 patients with SLE were tested for serum total PRL, serum free PRL, and PRL in fractions obtained after gel filtration chromatography (in 70 sera taken at random) by immunoradiometric assay based on disease activity. RESULTS: A significant correlation between direct PRL and free PRL levels was found in patients with and without lupus activity (r = 0.475, P<0.001); however, this was less so for non-active patients than for active patients (r=0.433, P<0.001 and r=0.909, P<0.001, respectively). SLE Disease Activity Index (SLEDAI) scores correlated positively with serum free PRL levels (r=0.314, P<0.001) and percentage of little PRL (r=0.33, P=0.005) and negatively with percentage of big big PRL (r=-0.3, P=0.012). Patients with active disease had higher serum free PRL levels (median 12.6 vs 9.3 ng/ml, P<0.001), higher percentages of little PRL (83.1 +/- 21.2 vs 63.6 +/- 24.8%, P=0.011) and lower percentages of big big PRL (9.4 +/- 18.0 vs 25.2 +/- 24.3%, P=0.031). Different clinical manifestations and serological parameters of lupus disease activity were more frequent in patients with free hyperprolactinaemia than in patients with normal serum free PRL levels (such as neurological manifestations, renal involvement, serositis, haematological manifestations, anti-double-stranded DNA and hypocomplementaemia; P<0.021). CONCLUSION: An increase in serum free PRL levels, higher percentages of little PRL and lower percentages of big big PRL proved to be factors related to lupus activity in a subset of patients with SLE. These novel data must be taken into account in future studies aiming to establish a relationship between PRL and disease activity in SLE.     

Outcomes of achieving lupus low disease activity state and damage accrual in childhood-onset systemic lupus erythematosus

Clinical Rheumatology - At present, the treat-to-target approach has been proposed with the lupus low disease activity state (LLDAS) as an achievable target. To determine damage accrual and...     

Predictors of neuropsychiatric damage in systemic lupus erythematosus: data from the Maryland lupus cohort

OBJECTIVE: To identify factors predictive of significant neuropsychiatric (NP) damage in systemic lupus erythematosus (SLE). METHODS: One hundred and thirty patients with SLE were followed at the University of Maryland Lupus Clinic from 1992 until 2003. NP manifestations were defined according to the revised American College of Rheumatology (ACR) nomenclature and case definitions for NP-SLE syndromes. Disease activity was measured using the SLE Disease Activity Index (SLEDAI), organ damage using the Systemic Lupus International Collaborating Clinics Damage Index SLICC/ACR (SDI); NP damage (NPDI) was measured with the corresponding domain of the SDI. At end of study period, 64 patients exhibited no NP damage (NPDI = 0) and 66 patients developed significant NP damage (defined as NPDI > or =1). The baseline features for these two patient groups were compared, and variables found to be significantly different were examined by multivariable analyses to determine their contribution to NP damage. RESULTS: Significant NP damage is common in SLE; mortality is infrequent and the cause of death is unrelated to NP damage. Independent predictors of significant NP damage were disease activity, Caucasian ethnicity and the presence of antiphospholipid antibodies and anti-Ro/SSA antibody. Certain clinical features at baseline predicted specific NP damage. For example, higher disease activity at baseline was predictive of psychosis and cognitive impairment, anti-dsDNA was predictive of polyneuropathy, and antiphospholipid antibodies were predictive of seizures and cerebrovascular accidents. CONCLUSIONS: In this longitudinal SLE cohort, significant cumulative NP damage occurred. Early aggressive therapy targeted towards NP manifestations may prevent the occurrence of NP damage.     

Phytohemagglutinin-stimulated lymphocytes from patients with systemic lupus erythematosus demonstrate DNA damage

DNA samples from control and lupus lymphocytes were studied for DNA integrity and single-strand breaks by agarose gel electrophoresis following digestion with the enzyme S1 nuclease. S1 nuclease digests single-strand gaps in double-stranded DNA. Gel patterns of phytohemagglutinin (PHA)-stimulated control and lupus lymphocyte DNAs were identical in the absence of S1 nuclease incubation. DNA isolated from PHA-stimulated control lymphocytes was relatively resistant to S1 nuclease digestion in 14 of 16 samples. However, 15 of 16 DNA samples from PHA-stimulated lupus lymphocytes demonstrated dramatically greater S1 nuclease digestion than paired control DNAs from lymphocytes analyzed at the same time under the same conditions. Increased S1 sensitivity suggests that more single-strand DNA breaks were found in PHA-stimulated lupus lymphocytes and/or the lupus DNA was more damaged than control DNA. We suggest that structural changes found in DNA from stimulated T lymphocytes of lupus patients are consistent with an endogenous antigen-mediated disorder.     

Low-binding alleles of Fcgamma receptor types IIA and IIIA are inherited independently and are associated with systemic lupus erythematosus in Hispanic patients

OBJECTIVE: To examine the relationship between allelic polymorphisms of IgG receptors (FcgammaR) and the development of lupus nephritis in a prospective study, and to determine the distribution of FcgammaR haplotypes (FcgammaRIIA and FcgammaRIIIA genotypes) in lupus patients and disease-free control subjects. METHODS: We studied 67 Hispanic systemic lupus erythematosus (SLE) patients from a prospective study of outcome and 53 disease-free control subjects. Patients were followed up longitudinally for 3 years. FcgammaRIIA and FcgammaRIIIA genotypes were determined using allele-specific polymerase chain reaction. RESULTS: Nephritis was present in 28% of patients at entry into the study and in 69% at the end of 3 years. In the nephritis group (n = 46), as well as the entire SLE cohort, there was a predominance of genotypes with low-binding alleles (FcgammaRIIa-R131 and FcgammaRIIIa-F176) at both loci (SLE nephritis patients 89% versus controls 62%; P < 0.002; odds ratio 0.20 [95% confidence interval 0.05-0.6] for risk of nephritis in individuals homozygous for either FcgammaRIIa-H131 or FcgammaRIIIaV176). The frequency of individuals homozygous for high-binding alleles at either locus decreased as the burden of disease increased (P < 0.002, by Mann-Whitney test). There was no linkage disequilibrium between FcgammaRIIA and FcgammaRIIIA in Hispanics, yet in the SLE patients, there was a clear overrepresentation of the FcgammaRIIa-R131;FcgammaRIIIa-F176 haplotype (SLE patients 48% versus controls 30%) and a decrease in the frequency of the high-binding haplotype (4% versus 23%) (P < 0.002). CONCLUSION: We observed an increase in the frequency of low-binding FcgammaR alleles in an SLE population with a high prevalence of renal disease. The apparent selection for the FcgammaRIIa-R131;FcgammaRIIIa-F176 haplotype in Hispanic patients suggests that low-binding alleles of both FcgammaRIIa and FcgammaRIIIa confer risk for SLE and may act additively in the pathogenesis of disease, whereas the high-binding haplotype FcgammaRIIa-H131;FcgammaRIIIa-V176 is protective, particularly in the homozygous state.