Distal urethral carcinoma: Contemporary management with phallus preserving techniques.

INTRODUCTION: Primary urethral carcinoma is a rare clinical entity with an incidence of 1 case per million in the United Kingdom. Cancers of the distal urethra are most commonly of squamous subtype and often associated with Human Papilloma Virus infection. Penile preserving techniques are recommended in tumours of the pendulous urethra with a number of surgical approaches described. Herein, we describe the surgical management of 7 patients presenting with primary urethral carcinoma. METHODS: Seven patients diagnosed with primary urethral carcinoma of the distal urethra were identified using a prospectively maintained penile cancer database at our institution from May 2017 to November 2020. RESULTS: The mean age at presentation was 56.5 (33-80) years. Presenting symptoms included visible lesion, LUTS and a groin mass. Three patients had lesions located within the glanular urethra and had a distal urethrectomy and primary closure. Two patients with lesions extending proximal to the glanular urethra and into or beyond the fossa navicularis had a distal urethrectomy with a hypospadic neomeatus formation. One patient with tumour extending into the glans penis underwent distal urethrectomy and partial glansectomy with split thickness skin graft. A partial penectomy was performed for one patient with urethral tumour invading the corporal heads. Mean follow-up was 23.4 (±17.0) months. There have been no disease recurrences to date. CONCLUSION: Penile preserving techniques are feasible in patients with tumours of the pendulous urethra and do not appear to compromise local control.

Assessment of referral patterns for boys with suspected undescended testes and identification of risk factors to aid diagnosis.

INTRODUCTION: Undescended testis (UDT) is a clinical diagnosis and a common reason for referral to paediatric urology outpatients. Our aim was to assess current referral patterns at our unit and to identify predictive factors that may better aid primary care physicians (PCP) in diagnosing UDT based on history and physical exam. METHODS: A retrospective analysis of referrals to outpatients from 2014 to 2016 was performed to assess current referral patterns including referral source, age, reason for referral and outcome following assessment by a single consultant paediatric urologist.A prospective analysis of new referrals was performed to identify predictive factors which may aid in the diagnosis of UDT including gestational age, presence of scrotal asymmetry and previously obtained imaging. RESULTS: From 2014 to 2016, 259 boys were referred with suspected UDT. The majority of referrals were received from PCPs (62%) followed by Neonatology (29%), Paediatrics (8%) and general surgery (1%). Median age at time of assessment was 29 (5-180) months. One hundred and eight (41.7%) boys were diagnosed with UDT.There were 74 boys assessed prospectively. Median age at assessment was 24.5 (6-171) months. We identified 3 predictors of a diagnosis of UDT; history of prematurity (p = 0.001), UDT mentioned to the parents at birth (p = 0.027) and scrotal asymmetry on examination (p < 0.001). Greatest diagnostic inaccuracy was found in boys referred beyond one year of age (27.7%). In this cohort, the absence of all three risk factors was associated with a negative predictive value of 94.1%. CONCLUSION: The majority of boys with suspected UDT are referred beyond the age recommended for orchidopexy (6-12 months). The majority of boys referred for assessment did not have UDT. We have identified three predictive factors that may aid referring physicians when assessing boys, particularly those older than 1 year.

Communication: Chemisorption of muonium on gold nanoparticles: A sensitive new probe of surface magnetism and reactivity.

Chemisorption of muonium onto the surface of gold nanoparticles has been observed. Muonium (µ+e-), a light hydrogen-like atom, reacts chemically with uncapped 7 nm gold nanoparticles embedded in mesoporous silica (SBA-15) with a strong temperature-dependent rate. The addition rate is fast enough to allow coherent spin transfer into a diamagnetic muon state on the nanoparticle surface. The muon is well established as a sensitive probe of static or slowly fluctuating magnetic fields in bulk matter. These results represent the first muon spin rotation signal on a nanoparticle surface or any metallic surface. Only weak magnetic effects are seen on the surface of these Au nanoparticles consistent with Pauli paramagnetism.

Genetic association of CD247 (CD3ζ) with SLE in a large-scale multiethnic study.

A classic T-cell phenotype in systemic lupus erythematosus (SLE) is the downregulation and replacement of the CD3ζ chain that alters T-cell receptor signaling. However, genetic associations with SLE in the human CD247 locus that encodes CD3ζ are not well established and require replication in independent cohorts. Our aim was therefore to examine, localize and validate CD247-SLE association in a large multiethnic population. We typed 44 contiguous CD247 single-nucleotide polymorphisms (SNPs) in 8922 SLE patients and 8077 controls from four ethnically distinct populations. The strongest associations were found in the Asian population (11 SNPs in intron 1, 4.99 × 10(-4) < P < 4.15 × 10(-2)), where we further identified a five-marker haplotype (rs12141731-rs2949655-rs16859085-rs12144621-rs858554; G-G-A-G-A; P(hap) = 2.12 × 10(-5)) that exceeded the most associated single SNP rs858554 (minor allele frequency in controls = 13%; P = 4.99 × 10(-4), odds ratio = 1.32) in significance. Imputation and subsequent association analysis showed evidence of association (P < 0.05) at 27 additional SNPs within intron 1. Cross-ethnic meta-analysis, assuming an additive genetic model adjusted for population proportions, showed five SNPs with significant P-values (1.40 × 10(-3) < P< 3.97 × 10(-2)), with one (rs704848) remaining significant after Bonferroni correction (P(meta) = 2.66 × 10(-2)). Our study independently confirms and extends the association of SLE with CD247, which is shared by various autoimmune disorders and supports a common T-cell-mediated mechanism.

Genetic analysis of the pathogenic molecular sub-phenotype interferon-alpha identifies multiple novel loci involved in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by inflammation of multiple organ systems and dysregulated interferon responses. SLE is both genetically and phenotypically heterogeneous, greatly reducing the power of case-control studies in SLE. Elevated circulating interferon-alpha (IFN-α) is a stable, heritable trait in SLE, which has been implicated in primary disease pathogenesis. About 40-50% of patients have high IFN-α, and high levels correspond with clinical differences. To study genetic heterogeneity in SLE, we performed a case-case study comparing patients with high vs low IFN-α in over 1550 SLE cases, including genome-wide association study and replication cohorts. In meta-analysis, the top associations in European ancestry were protein kinase, cyclic GMP-dependent, type I (PRKG1) rs7897633 (P(Meta) = 2.75 × 10(-8)) and purine nucleoside phosphorylase (PNP) rs1049564 (P(Meta) = 1.24 × 10(-7)). We also found evidence for cross-ancestral background associations with the ankyrin repeat domain 44 (ANKRD44) and pleckstrin homology domain containing, family F member 2 gene (PLEKHF2) loci. These loci have not been previously identified in case-control SLE genetic studies. Bioinformatic analyses implicated these loci functionally in dendritic cells and natural killer cells, both of which are involved in IFN-α production in SLE. As case-control studies of heterogeneous diseases reach a limit of feasibility with respect to subject number and detectable effect size, the study of informative pathogenic sub-phenotypes becomes an attractive strategy for genetic discovery in complex disease.

Effects of Stigmatization on Gay Men Living with HIV/AIDS in a Central-Eastern European Context: A Qualitative Analysis from Hungary.

This qualitative study highlights the social dynamics affecting people living with HIV (PLH) in Hungary and in the Central-Eastern European region. The study focused on the special needs and concerns of men living with HIV/AIDS as well as changes in their social relationships and institutional support provision, coping strategies and patterns of social functioning, especially in the context of social stigmatization. Consistent with international qualitative research findings in the field of HIV/AIDS prevention, the present study contributes to a fuller understanding of relationship between sexual behavior, HIV/AIDS related risks and risk perceptions as well as homosexuality-and HIV/AIDS stigma-related social exclusion in a previously under-researched socio-cultural setting. The findings of our study point to several barriers to effective HIV prevention, which should be overcome to improve the present situation by lessening the adverse effects of HIV/AIDS-and homosexuality-related stigma within the gay community, the general population and especially among service providers. One of the main barriers is the lack of public health programs specifically targeting MSM in Hungary, where the predominant mode of HIV transmission remains sex between men.

A functional haplotype of UBE2L3 confers risk for systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease with diverse clinical manifestations characterized by the development of pathogenic autoantibodies manifesting in inflammation of target organs such as the kidneys, skin and joints. Genome-wide association studies have identified genetic variants in the UBE2L3 region that are associated with SLE in subjects of European and Asian ancestry. UBE2L3 encodes an ubiquitin-conjugating enzyme, UBCH7, involved in cell proliferation and immune function. In this study, we sought to further characterize the genetic association in the region of UBE2L3 and use molecular methods to determine the functional effect of the risk haplotype. We identified significant associations between variants in the region of UBE2L3 and SLE in individuals of European and Asian ancestry that exceeded a Bonferroni-corrected threshold (P<1 × 10(-4)). A single risk haplotype was observed in all associated populations. Individuals harboring the risk haplotype display a significant increase in both UBE2L3 mRNA expression (P=0.0004) and UBCH7 protein expression (P=0.0068). The results suggest that variants carried on the SLE-associated UBE2L3 risk haplotype influence autoimmunity by modulating UBCH7 expression.

Role of MYH9 and APOL1 in African and non-African populations with lupus nephritis.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by autoantibody production and organ damage. Lupus nephritis (LN) is one of the most severe manifestations of SLE. Multiple studies reported associations between renal diseases and variants in the non-muscle myosin heavy chain 9 (MYH9) and the neighboring apolipoprotein L 1 (APOL1) genes. We evaluated 167 variants spanning MYH9 for association with LN in a multiethnic sample. The two previously identified risk variants in APOL1 were also tested for association with LN in European-Americans (EAs) (N = 579) and African-Americans (AAs) (N = 407). Multiple peaks of association exceeding a Bonferroni corrected P-value of P < 2.03 × 10(-3) were observed between LN and MYH9 in EAs (N = 4620), with the most pronounced association at rs2157257 (P = 4.7 × 10(-4), odds ratio (OR) = 1.205). A modest effect with MYH9 was also detected in Gullah (rs8136069, P = 0.0019, OR = 2.304). No association between LN and MYH9 was found in AAs, Asians, Amerindians or Hispanics. This study provides the first investigation of MYH9 in LN in non-Africans and of APOL1 in LN in any population, and presents novel insight into the potential role of MYH9 in LN in EAs.

The rs4774 CIITA missense variant is associated with risk of systemic lupus erythematosus.

The major histocompatibility complex (MHC) class II transactivator gene (CIITA) encodes an important transcription factor required for human leukocyte antigens (HLA) class II MHC-restricted antigen presentation. MHC genes, including the HLA class II DRB1*03:01 allele, are strongly associated with systemic lupus erythematosus (SLE). Recently the rs4774 CIITA missense variant (+1632G/C) was reported to be associated with susceptibility to multiple sclerosis. In the current study, we investigated CIITA, DRB1*03:01 and risk of SLE using a multi-stage analysis. In stage 1, 9 CIITA variants were tested in 658 cases and 1363 controls (N=2021). In stage 2, rs4774 was tested in 684 cases and 2938 controls (N=3622). We also performed a meta-analysis of the pooled 1342 cases and 4301 controls (N=5643). In stage 1, rs4774(*)C was associated with SLE (odds ratio (OR)=1.24, 95% confidence interval (95% CI)=1.07-1.44, P=4.2 × 10(-3)). Similar results were observed in stage 2 (OR=1.16, 95% CI=1.02-1.33, P=8.5 × 10(-3)) and the meta-analysis of the combined data set (OR=1.20, 95% CI=1.09-1.33, P(meta)=2.5 × 10(-4)). In all three analyses, the strongest evidence for association between rs4774(*)C and SLE was present in individuals who carried at least one copy of DRB1*03:01 (P(meta)=1.9 × 10(-3)). Results support a role for CIITA in SLE, which appears to be stronger in the presence of DRB1*03:01.

Evaluation of the TREX1 gene in a large multi-ancestral lupus cohort.

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disorder with a complex pathogenesis in which genetic, hormonal and environmental factors have a role. Rare mutations in the TREX1 gene, the major mammalian 3'-5' exonuclease, have been reported in sporadic SLE cases. Some of these mutations have also been identified in a rare pediatric neurological condition featuring an inflammatory encephalopathy known as Aicardi-Goutières syndrome (AGS). We sought to investigate the frequency of these mutations in a large multi-ancestral cohort of SLE cases and controls. A total of 40 single-nucleotide polymorphisms (SNPs), including both common and rare variants, across the TREX1 gene, were evaluated in ∼8370 patients with SLE and ∼7490 control subjects. Stringent quality control procedures were applied, and principal components and admixture proportions were calculated to identify outliers for removal from analysis. Population-based case-control association analyses were performed. P-values, false-discovery rate q values, and odds ratios (OR) with 95% confidence intervals (CI) were calculated. The estimated frequency of TREX1 mutations in our lupus cohort was 0.5%. Five heterozygous mutations were detected at the Y305C polymorphism in European lupus cases but none were observed in European controls. Five African cases incurred heterozygous mutations at the E266G polymorphism and, again, none were observed in the African controls. A rare homozygous R114H mutation was identified in one Asian SLE patient, whereas all genotypes at this mutation in previous reports for SLE were heterozygous. Analysis of common TREX1 SNPs (minor allele frequency (MAF)>10%) revealed a relatively common risk haplotype in European SLE patients with neurological manifestations, especially seizures, with a frequency of 58% in lupus cases compared with 45% in normal controls (P=0.0008, OR=1.73, 95% CI=1.25-2.39). Finally, the presence or absence of specific autoantibodies in certain populations produced significant genetic associations. For example, a strong association with anti-nRNP was observed in the European cohort at a coding synonymous variant rs56203834 (P=2.99E-13, OR=5.2, 95% CI=3.18-8.56). Our data confirm and expand previous reports and provide additional support for the involvement of TREX1 in lupus pathogenesis.

The effects of previous hysterectomy on lupus.

Hysterectomy is one of the most common surgical procedures performed in United States, and currently, one in three women in United States has had a hysterectomy by the age of 60 years. Systemic lupus erythematosus (SLE) is a common autoimmune disease and especially targets women of childbearing age at least 10 times higher than men, which reflects the major role of female sex hormones. In this retrospective study, we evaluate the potential effects of previous hysterectomy in our lupus cohort. Data collected from study subject questionnaires were obtained from the Lupus Family Registry and Repository (LFRR) at the Oklahoma Medical Research Foundation. Hysterectomy data were available from 3389 subjects. SLE patients with a positive history of hysterectomy have been selected and compared with matched lupus patients with a negative history of hysterectomy and healthy controls. Association analyses were performed, and the P values and adjusted odds ratios (ORs) were calculated. SLE patients with a negative history of hysterectomy more likely had kidney nephritis or positive anti-dsDNA than age-matched SLE patients with a history of hysterectomy before disease onset. This effect was independent of ethnicity with an OR of 6.66 (95% CI = 3.09-14.38, P = 1.00 x 10(-8)) in European patients and 2.74 (95% CI = 1.43-5.25, P = 0.001) in African-Americans. SLE patients with a positive history of hysterectomy before disease onset also had a later age of disease onset (P = 0.0001) after adjustment for age and race. Our findings support the notion that the influence of female sex hormones in SLE and various clinical findings are tremendous and that surgical menopause such as this could significantly affect the outcome of disease and clinical manifestations.

Recent insights into the genetic basis of systemic lupus erythematosus.

Genetic variation was first shown to be important in systemic lupus erythematosus (SLE or lupus) in the 1970s with associations in the human leukocyte antigen region. Almost four decades later, and with the help of increasingly powerful genetic approaches, more than 25 genes are now known to contribute to the mechanisms that predispose individuals to lupus. Over half of these loci have been discovered in the past 2 years, underscoring the extraordinary success of genome-wide association approaches in SLE. Well-established risk factors include alleles in the major histocompatibility complex region (multiple genes), IRF5, ITGAM, STAT4, BLK, BANK1, PDCD1, PTPN22, TNFSF4, TNFAIP3, SPP1, some of the Fcgamma receptors, and deficiencies in several complement components, including C1q, C4 and C2. As reviewed here, many susceptibility genes fall into key pathways that are consistent with previous studies implicating immune complexes, host immune signal transduction and interferon pathways in the pathogenesis of SLE. Other loci have no known function or apparent immunological role and have the potential to reveal novel disease mechanisms. Certainly, as our understanding of the genetic etiology of SLE continues to mature, important new opportunities will emerge for developing more effective diagnostic and clinical management tools for this complex autoimmune disease.

Identification of new SLE-associated genes with a two-step Bayesian study design.

In our earlier study, we utilized a Bayesian design to probe the association of approximately 1000 genes (approximately 10,000 single-nucleotide polymorphisms (SNPs)) with systemic lupus erythematosus (SLE) on a moderate number of trios of parents and children with SLE. Two genes associated with SLE, with a multitest-corrected false discovery rate (FDR) of <0.05, were identified, and a number of noteworthy genes with FDR of <0.8 were also found, pointing out a future direction for the study. In this report, using a large population of controls and adult- or childhood-onset SLE cases, we have extended the earlier investigation to explore the SLE association of 10 of these noteworthy genes (109 SNPs). We have found that seven of these genes exhibit a significant (FDR<0.05) association with SLE, both confirming some genes that have earlier been found to be associated with SLE (PTPN22 and IRF5) and presenting novel findings of genes (KLRG1, interleukin-16, protein tyrosine phosphatase receptor type T, toll-like receptor (TLR)8 and CASP10), which have not been reported earlier. The results signify that the two-step candidate pathway design is an efficient way to study the genetic foundations of complex diseases. Furthermore, the novel genes identified in this study point to new directions in both the diagnosis and the eventual treatment of this debilitating disease.

Evaluation of C1q genomic region in minority racial groups of lupus.

Complement cascade plasma proteins play a complex role in the etiopathogenesis of systemic lupus erythematosus (SLE). Hereditary C1q deficiency has been strongly related to SLE; however, there are very few published SLE studies that evaluate the polymorphisms of genes encoding for C1q (A, B and C). In this study, we evaluated 17 single nucleotide polymorphisms (SNPs) across 37 kb of C1QA, C1QB and C1QC in a lupus cohort of individuals of the African-American and Hispanic origin. In a case-only analysis, a significant association at multiple SNPs in the C1QA gene was detected in African Americans with kidney nephritis (best P=4.91 x 10(-6)). In addition, C1QA was associated with SLE in African Americans with a lack of nephritis and accompanying photosensitivity when compared with that in normal controls (P=6.80 x 10(-6)). A similar trend was observed in the Hispanic subjects (P=0.003). Quantitative analysis showed that some SNPs in C1q genes might be correlated with C3 complement levels in an additive model among African Americans (best P=0.0001). The C1QA gene is associated with subphenotypes of lupus in the African-American and Hispanic subjects. Further studies with higher SNP densities in this region and other complement components are necessary to elucidate the complex genetics and phenotypic interactions between complement components and SLE.

Replication of the BANK1 genetic association with systemic lupus erythematosus in a European-derived population.

Systemic lupus erythematosus (SLE) is an autoimmune disease with highly variable clinical presentation. Patients suffer from immunological abnormalities that target T-cell, B-cell and accessory cell functions. B cells are hyperactive in SLE patients. An adapter protein expressed in B cells called BANK1 (B-cell scaffold protein with ankyrin repeats) was reported in a previous study to be associated with SLE in a European population. The objective of this study was to assess the BANK1 genotype-phenotype association in an independent replication sample. We genotyped 38 single nucleotide polymorphisms (SNPs) in BANK1 on 1892 European-derived SLE patients and 2652 European-derived controls. The strongest associations with SLE and BANK1 were at rs17266594 (corrected P-value=1.97 x 10(-5), odds ratio (OR)=1.22, 95% CI 1.12-1.34) and rs10516487 (corrected P-value=2.59 x 10(-5), OR=1.22, 95% CI 1.11-1.34). Our findings suggest that the association is explained by these two SNPs, confirming previous reports that these polymorphisms contribute to the risk of developing lupus. Analysis of patient subsets enriched for hematological, immunological and renal ACR criteria or the levels of autoantibodies, such as anti-RNP A and anti-SmRNP, uncovers additional BANK1 associations. Our results suggest that BANK1 polymorphisms alter immune system development and function to increase the risk for developing lupus.

Meta-analysis and imputation identifies a 109 kb risk haplotype spanning TNFAIP3 associated with lupus nephritis and hematologic manifestations.

TNFAIP3 encodes the ubiquitin-modifying enzyme, A20, a key regulator of inflammatory signaling pathways. We previously reported association between TNFAIP3 variants and systemic lupus erythematosus (SLE). To further localize the risk variant(s), we performed a meta-analysis using genetic data available from two Caucasian case-control datasets (1453 total cases, 3381 total control subjects) and 713 SLE trio families. The best result was found at rs5029939 (P=1.67 x 10(-14), odds ratio=2.09, 95% confidence interval 1.68-2.60). We then imputed single nucleotide polymorphisms (SNPs) from the CEU Phase II HapMap using genotypes from 431 SLE cases and 2155 control subjects. Imputation identified 11 SNPs in addition to three observed SNPs, which together, defined a 109 kb SLE risk segment surrounding TNFAIP3. When evaluating whether the rs5029939 risk allele was associated with SLE clinical manifestations, we observed that heterozygous carriers of the TNFAIP3 risk allele at rs5029939 have a twofold increased risk of developing renal or hematologic manifestations compared to homozygous non-risk subjects. In summary, our study strengthens the genetic evidence that variants in the region of TNFAIP3 influence risk for SLE, particularly in patients with renal and hematologic manifestations, and narrows the risk effect to a 109 kb DNA segment that spans the TNFAIP3 gene.

Genetic associations of LYN with systemic lupus erythematosus.

We targeted LYN, a src-tyosine kinase involved in B-cell activation, in case-control association studies using populations of European-American, African-American and Korean subjects. Our combined European-derived population, consisting of 2463 independent cases and 3131 unrelated controls, shows significant association with rs6983130 in a female-only analysis with 2254 cases and 2228 controls (P=1.1 x 10(-4), odds ratio (OR)=0.81 (95% confidence interval: 0.73-0.90)). This single nucleotide polymorphism (SNP) is located in the 5' untranslated region within the first intron near the transcription initiation site of LYN. In addition, SNPs upstream of the first exon also show weak and sporadic association in subsets of the total European-American population. Multivariate logistic regression analysis implicates rs6983130 as a protective factor for systemic lupus erythematosus (SLE) susceptibility when anti-dsDNA, anti-chromatin, anti-52 kDa Ro or anti-Sm autoantibody status were used as covariates. Subset analysis of the European-American female cases by American College of Rheumatology classification criteria shows a reduction in the risk of hematological disorder with rs6983130 compared with cases without hematological disorders (P=1.5 x 10(-3), OR=0.75 (95% CI: 0.62-0.89)). None of the 90 SNPs tested show significant association with SLE in the African American or Korean populations. These results support an association of LYN with European-derived individuals with SLE, especially within autoantibody or clinical subsets.

Patients with familial and sporadic onset SLE have similar clinical profiles but vary profoundly by race.

Few large, multi-ethnic studies have examined the clinical and serologic differences between familial and sporadic SLE patients. Understanding these similarities and differences is critical for interpreting genetic studies and developing therapeutic strategies. We compiled information on 1915 patients with SLE in a large multi-racial cohort, including general demographics, pedigree structure and the specific American College of Rheumatology (ACR) criteria met. One patient was randomly selected from each multiplex family for analysis, yielding 554 European-Americans (EA), 373 African-Americans (AA), 193 Hispanics (HI) and 237 patients of other of mixed races. When comparing familial and sporadic patients stratified by race, lupus erythematosus (LE) cells and arthritis were increased in white familial cases (P = 5.5 x 10(-6) and P = 0.028, respectively), but no other significant differences between familial and sporadic patients were found. We found that there were profound differences in clinical profiles between races. For example, photosensitivity and malar rash were decreased in AA (P = 1.3 x 10(-13) and 1.4 x 10(-7), respectively), whereas discoid rash was increased in AA (P = 5.5x10(-6)). EA had significantly less renal disease (P = 5.4x10(-13)), proteinuria (P = 4 x 10(-12)) and anti-Sm (P = 1.7 x 10(-12)) than AA or HI. We, therefore, conclude that familial and sporadic onset patients may be treated similarly with respect to clinical and genetic studies.

Haemolytic anaemia in a multi-ethnic cohort of lupus patients: a clinical and serological perspective.

Systemic lupus erythematosus is a chronic autoimmune disease that can be associated with a variety of haematological manifestations. We identified 76 patients with haemolytic anaemia in a cohort of 1251 unrelated female lupus patients enrolled in our studies. The presence of the various American College of Rheumatology clinical criteria for lupus and serological specificities were determined in lupus patients with haemolytic anaemia and compared with a group of race-matched control lupus patients without haemolytic anaemia. Clinical data were obtained from medical records, and serological specificities were determined in our clinical immunology laboratory at OMRF. The presence of haemolytic anaemia in lupus patients was associated with a higher frequency of proteinuria (OR = 2.70, P = 0.000031), urinary cellular casts (OR = 2.83, P = 0.000062), seizures (OR = 2.96, P = 0.00024), pericarditis (OR = 2.21, P = 0.0019), pleuritis (OR = 1.72, P = 0.028) and lymphopenia (OR = 1.79, P = 0.015). These findings were independent of the presence of thrombocytopenia, which was approximately five times more common in lupus patients with haemolytic anaemia. Lupus patients with haemolytic anaemia were about 8 years younger than lupus patients without haemolytic anaemia at the time of disease onset (P = 0.000001). In the absence of thrombocytopenia, lupus patients with haemolytic anaemia were approximately two times more likely to have anti-dsDNA antibodies (P = 0.024). The presence of haemolytic anaemia is associated with a subset of lupus characterized by a younger age of disease onset, and a more severe disease with a higher likelihood of renal involvement, seizures, serositis and other cytopenias.