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Co-occurrence of autoimmune diseases (ADs) within an individual is postulated to be a frequent phenomenon in rheumatic diseases. Similar clinical signs and symptoms, pathophysiological mechanisms, genetic factors within autoimmune diseases and aggregation of diverse ADs within families sustain the theory of shared pathogenesis of several ADs (autoimmune tautology). Polyautoimmunity (PA) is defined as the presence of more than one autoimmune disease in a single patient. When three or more autoimmune diseases coexist, this condition is called multiple autoimmune syndrome (MAS). This analysis summarizes an estimated prevalence of PA in the most common rheumatic diseases, the presumable risk factors for PA and influence of concomitant diseases on the course of disease.

Autoimmune diseases (AD) are responsible for a substantial amount of disability and morbidity worldwide. Research generally focuses on a single disease, although autoimmune phenotypes could represent pleiotropic outcomes of non-specific disease genes underlying similar immunogenetic mechanisms. This report examined the effect and importance of the homozygosity status, using genome-wide interspersed markers, in individuals and multiplex families affected with AD. This study presented two approaches: (I) a case-control comparison and evaluation on the effect of homozygosity at the genome-wide level and per marker, including 453 unrelated individuals (121 late-, 79 early-onset AD, 40 polyautoimmunity (PolyA), 30 multiple autoimmune syndrome (MAS) and 183 healthy control individuals); and (II) a model-free affected pair linkage approach which included 35 MAS, 49 polyA, 104 late-, and 83 early-onset multiplex families. A total of 372 genome-wide markers were used in the analysis. The standardized observed homozygosity (SOH) was calculated and the association of the homozygosity status and the autoimmune trait was evaluated. The multipoint model-free linkage analysis was applied by using RELPAL from S.A.G.E v6.3. Results for the SOH showed significant differences between controls and early-onset individuals, where early-onset affected individuals showed lower homozygosity relative to controls. No differences were observed relative to controls for MAS, polyA and late-onset disease at the genome-wide level. The local marker homozygosity effect showed share and specific risk and/or protective effects for 24 markers. The model-free affected pair linkage approach lacked any suggestive linkage signals, but marginal signals displayed excess allele sharing for extreme phenotypes in autoimmunity. This study presumed autoimmunity as a trait rather than a clinical phenotype and tried to approach AD as a continuous trait presenting extreme phenotypes. Future approaches would be expected to dwell on the data presented here to corroborate and expand on sample size, marker coverage and their effects.

Objectives Familial autoimmunity and polyautoimmunity represent extreme phenotypes ideal for identifying major genomic variants contributing to autoimmunity. Whole exome sequencing (WES) and linkage analysis are well suited for this purpose due to its strong resolution upon familial segregation patterns of functional protein coding and splice variants. The primary objective of this study was to identify potentially autoimmune causative variants using WES data from extreme pedigrees segregating polyautoimmunity phenotypes. Methods DNA of 47 individuals across 10 extreme pedigrees, ascertained from probands affected with polyautoimmunity and familial autoimmunity, were selected for WES. Variant calls were obtained through Genome Analysis Toolkit. Filtration and prioritization framework to identify mutation(s) were applied, and later implemented for genetic linkage analysis. Sanger sequencing corroborated variants with significant linkage. Results Novel and mostly rare variants harbored in SRA1, MLL4, ABCB8, DHX34 and PLAUR showed significant linkage (LOD scores are >3.0). The strongest signal was in SRA1, with a LOD score of 5.48. Network analyses indicated that SRA1 , PLAUR and ABCB8 contribute to regulation of apoptotic processes. Conclusions Novel and rare variants in genetic linkage with polyautoimmunity were identified throughout WES. Genes harboring these variants might be major players of autoimmunity.

Objective.To assess the prevalence of autoimmune diseases in first-degree relatives of patients with systemic sclerosis (SSc), and to compare those results with control families in order to identify patterns of autoimmune diseases in relatives.Methods.A retrospective case-control postal questionnaire survey was performed in France to recruit patients with SSc belonging to an association of patients with SSc and unrelated age-matched and sex-matched controls. Each participant was asked to self-report on the existence of autoimmune diseases in their first-degree relatives. The prevalence of autoimmune diseases in the families of patients with SSc was compared with the corresponding prevalence in the families of controls.Results.A total of 121 families out of 373 (32.4%) with a member having SSc reported at least 1 autoimmune disease in 1 or more first-degree relatives. The most frequent autoimmune diseases in SSc families when adjusted for family size were autoimmune thyroid disease (AITD; 4.9%), rheumatoid arthritis (4.1%), psoriasis (3.9%), and type 1 diabetes mellitus (2.9%). Compared with control families, AITD and connective tissue diseases (SSc, systemic lupus erythematosus, or Sjögren’s syndrome) were more likely to occur in families with SSc (p = 0.01 and p = 0.01, respectively), with OR of 3.20 (95% CI 1.25–8.18) and 5.20 (95% CI 1.22–21.8). In contrast, inflammatory bowel disease was less likely to occur within families with SSc (p = 0.02, OR 0.29, 95% CI 0.11–0.80). In addition, the coexistence of more than 1 autoimmune disease in the index SSc case was associated with familial aggregation of autoimmune diseases.Conclusion.Our results show that autoimmune diseases cluster within families of patients with SSc. This supports the notion that these diseases might arise on a shared genetic basis underlying several autoimmune phenotypes.

Introducción: Las enfermedades autoinmunes (EA) son responsables de una gran porción de discapacidad y morbilidad a nivel mundial. Generalmente, las investigaciones científicas se centran en una sola enfermedad, aunque los fenotipos autoinmunes podrían estar representados por efectos pleiotrópicos en genes no-específicos al presentar mecanismos inmunogenéticos similares. Múltiples casos de una sola enfermedad dentro de familia son evidentes, y aún más sorprendente son los individuos en aquellas familias que sufren de múltiples enfermedades autoinmunes. Este estudio exploró la dinámica de agregación familiar y la segregación en pacientes con EA, poliautoimmunidad (polyA) (presentar por lo menos dos AD) y el síndrome autoinmune múltiple (MAS) (presentar tres o más EA). Por otra parte, se examinó el efecto y la importancia de la homocigosis y la ancestría en individuos afectados colombianos con respecto a desarrollar una EA. Métodos: La agregación y segregación familiar se examinó en familiares de primer grado para un rasgo binario en 210 familias afectadas por EA. La homocigosis se estudió en dos enfoques: (I) Comparación de casos y controles mediante la evaluación del efecto de la homocigosis al nivel de todo el genoma en 453 individuos no relacionados (121 EA tardía, 79 EA temprana, 40 polyA, 30 MAS y 183 individuos control); (II) por un estudio de ligamiento no-paramétrico en parientes afectados en 35 familias con MAS, 49 con polyA, 104 con EA tardía, y 83 con EA temprana. La ancestría se examinó en todos los individuos afectados y sanos colombianos, así como individuos originados a partir de poblaciones de referencia, suponiendo tres grupos ancestrales (k = 3) (i.e., europea, amerindia y africana). El efecto de ancestría para los rasgos estudiados se comparó y analizó mediante regresión logística con respecto a los controles. Todos los individuos y las familias fueron tratados e invitados a participar en el Centro de Investigación de Enfermedades Autoinmunes (CREA) en Medellín y Bogotá, Colombia. Resultados: Este proyecto sugiere que las EA no son rasgos independientes y que el género, la edad y la edad de inicio representan factores que definen y permiten el estudio de la dinámica de los rasgos dentro del grupo familiar. Más allá, los datos de segregación proporcionaron soporte para el papel del componente genético en la etiología de las EAs en las familias de aparición tardía, mientras que para las familias de inicio temprano no se observó un papel claro, tal vez debido a la edad relativamente joven familiar. Los datos también mostraron diferencias en la homocigosidad en relación con los controles para las personas de aparición temprana, mientras que en la inspección de varios marcadores locales se sugiere que la homocigosis se encuentra asociada con la protección/susceptibilidad para la EA temprana, de inicio tardío, polyA y MAS. Por otra parte, la ancestría y la autoinmunidad en muestras de colombianos mostraron cómo el paisaje rasgo autoinmune no es un escenario blanco y negro, sino más bien una colorida mezcla de factores genéticos y ambientales. Todos los marcadores analizados fueron muy informativos con una baja frecuencia del alelo nulo haciéndolos óptimos y fiables para estudios de diversidad genética. Conclusiones: Este estudio asumió a la autoinmunidad como un rasgo más que un fenotipo clínico y como un rasgo continuo que presenta fenotipos extremos. Los datos sugieren que las EAs no son independientes. Por último, una EA individual, definida por síntomas y signos, podría no ser completamente yuxtapuesta con una EA definida por el medio ambiente y genética, lo que hace aún más difícil la tarea de definir y dilucidar los mecanismos de las enfermedades. Background: Autoimmune diseases (AD) are responsible for a substantial amount of disability and morbidity worldwide. Research generally focuses on a single disease, although autoimmune phenotypes could represent pleiotropic outcomes of non-specific disease genes underlying similar immunogenetic mechanisms. While it is apparent that multiple cases of a single disease cluster within families, more striking are the individuals in those families afflicted with multiple autoimmune diseases. This study explored the dynamics of familial aggregation and segregation in AD (i.e., having at least one AD), polyautoimmunity (polyA) (i.e., having at least two ADs) and multiple autoimmune syndrome (MAS) (i.e., having three or more ADs) patients. Moreover, this project examined the effect and importance of homozygosity and whether the ancestry component of Colombian affected individuals is associated with susceptibility/protection to develop an AD. Methods: Familial aggregation was examined for first-degree relatives. Segregation analysis for a binary trait was implemented on 210 single ascertained multiplex AD families. Homozygosity was examined by two approaches: (I) a case – control comparison and evaluation on the effect of homozygosity at the genome-wide level, including 453 genotyped unrelated individuals (121 late-onset AD, 79 early-onset, 40 polyA, 30 MAS and 183 healthy control individuals); and (II) a model-free affected pair linkage approach which included 35 MAS, 49 polyA, 104 late-, and 83 early-onset multiplex families. The admixture effect was examined in all included Colombian affected and healthy individuals, as well as in the individuals originated from reference populations, assuming three ancestral groups (k=3) (i.e., European, Amerindian and African). The ancestry component effect for the studied traits was compared and examined by logistic regression relative to controls. All individuals and families were treated and recruited at the Center for Autoimmune Diseases Research (CREA) from Medellin and Bogota, Colombia, South America. Results: This project provided data supporting that polyA and MAS are not AD independent traits and that gender, age and age of onset represent factors that define and allow the study of the dynamics of the traits within the familial group. Also, segregation data provided evidence for the genetic component role in the etiology of AD in late-onset families, while for early-onset families and perhaps because of their the relatively familial young status, eluded a clear picture of autoimmunity segregation and aggregation. The data also showed homozygosity differences relative to controls for early-onset individuals, while on local inspection several markers suggested homozygosity associated with protection/susceptibility to early-, late-onset, polyA and/or MAS. Moreover, ancestry and autoimmunity in Colombian samples showed how the autoimmune trait landscape is not a black and white scenario but rather a colorful mix of genetic and environmental factors. All markers analyzed were highly informative with a low null allele frequency making them optimal and reliable for genetic diversity studies. Conclusions: This study presumed autoimmunity as a trait rather than a clinical phenotype and tried to approach AD as a continuous trait presenting extreme phenotypes. Data suggested that AD are not independent traits and that gender, age and age of onset represent factors play a role and allow to study of the dynamic of the traits. Finally, a clinical defined individual AD, defined by symptoms and signs, might not be completely juxtaposed to the AD trait defined by environment and genetics, which makes even more difficult the task to define and untangle disease mechanisms. Center for Autoimmune Disease Research (CREA)

Three related lines of evidence sustain the common origin for autoimmune diseases (ADs). First, the clinical evidence corresponding to the kaleidoscope of autoimmunity, which is the co-occurrence of various ADs within an individual or co-occurrence within members of a nuclear family. Second, the physiopathologic evidence indicating that the pathologic mechanisms might be similar among ADs. Lost, the genetic evidence indicating that autoimmune phenotypes could represent pleiotropic outcomes of nonspecific disease genes. The two conditions that better illustrate the kaleidoscope of autoimmunity are multiple autoimmune syndromes and familial autoimmunity. The multiple autoimmune syndromes consist of the presence of three or more well-defined autoimmune conditions in a single patient. The familial autoimmunity is defined as the presence of diverse ADs on multiple members of a nuclear family. Herein, both the multiple autoimmune syndromes and familial autoimmunity are discussed and various epidemiological factors considered in the context of the common genetic background of autoimmunity. © 2007 Future Drugs Ltd.

Introduction: Systemic sclerosis (SSc) is a connective tissue disease of unknown etiology, characterized by a triad of vascular injury, autoimmunity and tissue fibrosis. It is known that a positive family history is the greatest risk factor already identified for the development of SSc in a given individual. Preliminary observation of a high prevalence of polyautoimmunity and of familial autoimmunity in SSc patients support the idea that different autoimmune phenotypes may share common susceptibility variants. Objectives: To describe the frequency of familial autoimmunity and polyautoimmunity in 60 SSc patients in the Midwest region of Brazil, as well as to report the main autoimmune diseases observed in this association of comorbidities. Methods: A cross-sectional study with recruitment of 60 consecutive patients selected at the Rheumatology Department, University Hospital, Medicine School, Federal University of Mato Grosso do Sul (FMUFMS), as well as interviews of their relatives during the period from February 2013 to March 2014. Results: A frequency of 43.3% of polyautoimmunity and of 51.7% of familial autoimmunity in SSc patients was found. Patients with the presence of polyautoimmunity and familial autoimmunity presented primarily the diffuse form of SSc, but this indicator did not reach statistical significance. The autoimmune diseases most frequently observed in polyautoimmunity patients were: Hashimoto's thyroiditis (53.8%), Sjögren's syndrome (38.5%), and inflammatory myopathy (11.5%). The main autoimmune diseases observed in SSc patients' relatives were: Hashimoto's thyroiditis (32.3%), rheumatoid arthritis (22.6%), and SLE (22.6%). The presence of more than one autoimmune disease in SSc patients did not correlate with disease severity or activity. Conclusions: From the high prevalence of coexisting autoimmune diseases found in SSc patients, we stress the importance of the concept of shared autoimmunity, in order to promote a continued vigilance and promptly diagnose other possible autoimmune disease in patients, or in their kin. RESUMO Introdução: A esclerose sistêmica (ES) é uma enfermidade do tecido conjuntivo de etiologia desconhecida, caracterizada pela tríade de injúria vascular, autoimunidade e fibrose tecidual. Sabe-se que uma história familiar positiva representa o maior fator de risco já identificado para o desenvolvimento da ES em um determinado indivíduo. Observação prévia de alta prevalência de poliautoimunidade e de autoimunidade familiar em pacientes com ES reforça a ideia de que fenótipos autoimunes distintos podem dividir variantes comuns de susceptibilidade. Objetivos: Descrever a frequência de autoimunidade familiar e de poliautoimunidade em 60 pacientes com ES da região Centro-Oeste do Brasil, bem como relatar as principais doenças autoimunes observadas nessa associação de comorbidades. Métodos: Estudo transversal com recrutamento de 60 pacientes consecutivos, selecionados no Serviço de Reumatologia do Hospital Universitário da Faculdade de Medicina da Universidade Federal de Mato Grosso do Sul (FMUFMS), bem como entrevista de seus parentes, de fevereiro de 2013 a março de 2014. Resultados: Foi encontrada uma frequência de 43,3% de poliautoimunidade e de 51,7% de autoimunidade familiar nos pacientes com ES. Os pacientes com presença de poliautoimunidade e de autoimunidade familiar eram principalmente da forma difusa de ES, porém esse índice não atingiu significância estatística. As doenças autoimunes mais comumente observadas nos pacientes com poliautoimunidade foram: tireoidite de Hashimoto (53,8%), síndrome de Sjögren (38,5%) e miopatia inflamatória (11,5%). As principais doenças autoimunes observadas nos parentes dos pacientes com ES foram: tireoidite de Hashimoto (32,3%), artrite reumatoide (22,6%) e LES (22,6%). A presença de mais de uma enfermidade autoimune em pacientes com ES não se correlacionou com maior gravidade ou atividade da doença. Conclusões: A partir da alta prevalência encontrada de doenças autoimunes coexistentes em pacientes com ES, salientamos a importância do conceito de autoimunidade compartilhada, de forma a promover uma vigilância constante e diagnosticar prontamente uma possível outra doença autoimune nos pacientes ou em seus parentes.

Since cardiovascular disease (CVD) is the most common cause of mortality in patients with rheumatoid arthritis (RA), we aimed to determine factors associated with such a complication in a large series of Colombian patients. This was a cross-sectional analytical study in which 800 consecutive Colombian patients with RA were assessed for variables associated with CVD. Furthermore, a systematic literature review was performed to address the state of the art about non-traditional risk factors for CVD in RA. The preferred reporting items for systematic reviews and meta-analyses guidelines were followed in data extraction, analysis, and reporting of articles selected. Hypercholesterolemia, type 2 diabetes mellitus, abnormal body mass index, abdominal obesity, and current smoking were all traditional risk factors significantly associated with CVD in Colombians. As non-traditional risk factors, familial autoimmunity, more than 10 years of duration of the disease, patients working on household duties, use of systemic steroids, and low education level were associated with CVD in the studied population. Out of a total of 9,812 articles identified in PubMed and Scopus databases, 140 fulfilled the eligibility criteria and were included. Through this systematic review, several factors and outcomes related to CVD were confirmed and identified. These were categorized into genetics, RA-related, and others. Traditional risk factors do not completely explain the high rates of CVD in patients with RA; thus, novel risk factors related to autoimmunity are now recognized predicting the presence of CVD as strong as traditional risk factors. Our results may assist health professionals and policymakers in making decisions about CVD in patients with RA. © 2013 Springer Science+Business Media New York.

The fact that autoimmune diseases share subphenotypes, physiopathological mechanisms and genetic factors has been called autoimmune tautology, and indicates that they have a common origin. The autoimmune phenotypes vary depending on the target cell and the affected organ, gender, ancestry, trigger factors and age at onset. Ten shared characteristics supporting this logical theory are herein reviewed. © 2012 Elsevier B.V.

Similar pathophysiological mechanisms within autoimmune diseases have stimulated searches for common genetic roots. Polyautoimmunity is defined as the presence of more than one autoimmune disease in a single patient. When three or more autoimmune diseases coexist, this condition is called multiple autoimmune syndrome (MAS). We analyzed the presence of polyautoimmunity in 1,083 patients belonging to four autoimmune disease cohorts. Polyautoimmunity was observed in 373 patients (34.4%). Autoimmune thyroid disease (AITD) and Sjögren's syndrome (SS) were the most frequent diseases encountered. Factors significantly associated with polyautoimmunity were female gender and familial autoimmunity. Through a systematic literature review, an updated search was done for all MAS cases (January 2006–September 2011). There were 142 articles retrieved corresponding to 226 cases. Next, we performed a clustering analysis in which AITD followed by systemic lupus erythematosus and SS were the most hierarchical diseases encountered. Our results indicate that coexistence of autoimmune diseases is not uncommon and follows a grouping pattern. Polyautoimmunity is the term proposed for this association of disorders, which encompasses the concept of a common origin for these diseases.

Although autoimmune diseases exhibit contrasting epidemiological features, pathology, and clinical manifestations, three lines of evidence demonstrate that these diseases share similar immunogenetic mechanisms (that is, autoimmune tautology). First, clinical evidence highlights the co-occurrence of distinct autoimmune diseases within an individual (that is, polyautoimmunity) and within members of a nuclear family (that is, familial autoimmunity). Second, physiopathologic evidence indicates that the pathologic mechanisms may be similar among autoimmune diseases. Lastly, genetic evidence shows that autoimmune phenotypes might represent pleiotropic outcomes of the interaction of non-specific disease genes.

Juvenile idiopathic arthritis (JIA) is an autoimmune (AI) disease characterized by chronic arthritis in children. Children with JIA have increased prevalence of other AI diseases. Furthermore, relatives of children with JIA have been shown to have an increased prevalence of AI diseases. Our objective was to determine if there were differences in the prevalence of AI diseases among maternal and paternal relatives of children with JIA. Information about AI diseases among all living first- and second-degree relatives was collected by structured interviews with families of 121 simplex JIA families, 23 multiplex JIA families, and 45 control families. Overall, the prevalence of AI diseases was significantly increased among maternal second-degree relatives of cases compared to that of maternal second-degree relatives of controls [14% vs. 4.3%; p < 0.001]. The prevalence of AI diseases among mothers of JIA cases was three times that of fathers [32.3% vs. 11.4%; p < 0.0001]. The prevalence of AI diseases among all maternal second-degree relatives of children with JIA was significantly higher than that of all paternal second-degree relatives [14% vs. 7.9%; p < 0.004]. Although additional paternal effects cannot be excluded, together these results demonstrate that maternal relatives of children with JIA have an increased prevalence of autoimmunity compared to paternal relatives, suggesting that there might be a maternal parent-of-origin effect in JIA.

Objectives. Increased prevalence of familial autoimmune disease is a common finding among probands with various autoimmune disorders. Autistic disorder (autism) is a highly genetic disorder with known immune and immunogenetic abnormalities. Previous research has found an increased frequency of autoimmune disorders in families with autistic probands. We further investigated this association by determining the frequency of autoimmune disorders in families that have probands with pervasive developmental disorders (PDDs), including autism, compared with 2 control groups.Methods. Three well-defined study groups, including 1) families that have a child with a PDD, 2) families that have a child with an autoimmune disorder, and 3) families with a healthy control child, constituted the sample. A questionnaire inquiring about which first- and second-degree family members had received a diagnosis of having specific autoimmune disorders was completed by 101 families in each group.Results. The frequency of autoimmune disorders was significantly higher in families of the PDD probands compared with families of both the autoimmune and healthy control probands. Autoimmunity was highest among the parents of PDD probands compared with parents of the healthy control subjects. Hypothyroidism/Hashimoto’s thyroiditis and rheumatic fever were significantly more common in families with PDD probands than in the healthy control families.Conclusions. Autoimmunity was increased significantly in families with PDD compared with those of healthy and autoimmune control subjects. These preliminary findings warrant additional investigation into immune and autoimmune mechanisms in autism.

The objective of this multicentric case-control study was to investigate if a history of autoimmune disease (AD) in first-degree relatives (FDR) is a risk factor for systemic lupus erythematosus (SLE) and to evaluate the risk of AD among FDR of SLE patients. Cases were Italian SLE patients consecutively enrolled. Controls were orthopaedic inpatients without any autoimmune diseases.The strength of the association between family history of AD and SLE was measured as an odds ratio (OR) calculated from the coefficient of an unconditional regression model. To calculate the risk of AD among FDR of SLE patients, the extended generalized estimating equation technique was used. In total, 154 SLE cases and 140 controls were enrolled. A family history of AD was reported by 22.7% of SLE patients and by 5.7% of the controls. The risk of SLE increased with the number of FDR with AD (one FDR affected, OR 4.1; two or more, OR 11.3). The probability of having AD was higher among FDR of SLE cases in comparison to FDR of controls (RR 4.6; 95%CI 1.9-11.1). A female SLE patient conferred an increased risk of AD to her FDR; this risk is doubled in females (OR 10.3; 95% CI 3.1-34.4).

Objectives To identify polyautoimmunity and to search for a grouping pattern of autoimmune diseases (ADs). Methods This was a cross-sectional analytical study in which 1083 consecutive patients with rheumatoid arthritis (n=304), systemic lupus erythematosus (SLE, n=335), systemic sclerosis (n=290), and multiple sclerosis (n=154) were assessed for the coexistence of 23 ADs. Factors associated with polyautoimmunity were evaluated by multivariate analyses. A systematic literature review was done for all multiple autoimmune syndrome (MAS) cases up to 2011, which were analyzed using a distance measure adapted from the Rogers and Tanimoto coefficient for symmetric binary data. Then, clusters were obtained by using the hclust function implemented in R software. Results Polyautoimmunity was observed in 373 patients (34.4%). Autoimmune thyroid disease (AITD) and Sjogren’s syndrome (SS) were the most frequent diseases encountered. Female gender and familial autoimmunity were associated with polyautoimmunity. A dendogram based on 226 MAS cases from 142 articles retrieved was built (figure). AITD followed by SLE and SS were the most hierarchical diseases encountered and thus the most representatives of polyautoimmunity. Conclusions Results indicate that coexistence of ADs is not uncommon and follows a grouping pattern. Polyautoimmunity is the term proposed for this association of disorders, which encompasses the concept of a common origin for these diseases. It is our contention that the term “secondary diseases” should not longer be used because it detracts from the reality that these patients have two or more well-established ADs sharing the same etiopathogenesis. Disclosure of Interest None Declared

The prevalence of thyroid disease in 134 children, adolescents, and young adults with diabetes mellitus beginning in childhood is described. Clustering of a family history of thyroid disease and the presence of thyrogastric antibodies in some patients supports the concept of familial autoimmunity. In 4 children a diagnosis of hypothyroidism had already been made, one of whom had shown marked faltering of growth. In a further 3 there was evidence of previously unrecognised subclinical hypothyroidism but the growth of 2 of them had been good. The findings of this study indicate that while subclinical hypothyroidism should be considered in a diabetic whose growth is faltering, it is rarely a cause of such growth failure.

Background A high prevalence of autoimmune disease (AD) has been documented in relatives of adult patients with systemic lupus erythematosus (SLE). However, data on familial inheritance patterns in pediatric SLE patients is scarce. Findings The charts of 69 patients with pediatric-onset SLE were reviewed retrospectively. The primary aim was to describe the prevalence and types of AD in relatives of children with SLE. The secondary aims were: 1) to compare severity of SLE in children with and without relatives affected by AD, and 2) to evaluate the impact of baseline demographics on severity of SLE in subjects. At diagnosis, 42% of subjects had one or more first, second, or third degree relative(s) with AD; and 32% of subjects had one or more first degree relative(s) with AD. The most common diseases in relatives of children with SLE were SLE (21%) and thyroid disease (15%). Subjects with no family history of AD were more likely to have severe SLE. SLE severity in subjects did not differ by gender. Children presenting with SLE at an earlier age were found to have more severe disease. Conclusions This study demonstrated a high prevalence of AD in families of children with SLE, although a family history of AD did not correlate with more severe SLE in subjects. Future larger studies are necessary to elucidate patterns of familial inheritance and baseline patient characteristics that may affect severity of disease in pediatric SLE.