Changes in social isolation and loneliness following total hip and knee arthroplasty: longitudinal analysis of the English Longitudinal Study of Ageing (ELSA) cohort.

OBJECTIVE: To determine the prevalence and change in social isolation and loneliness in people before and after total hip arthroplasty (THA) and total knee arthroplasty (TKA) in England. DESIGN: The English Longitudinal Study of Ageing (ELSA) dataset, a prospective study of community-dwelling older adults, was used to identify people who had undergone primary THA or TKA because of osteoarthritis. Social isolation was assessed using the ELSA Social Isolation Index. Loneliness was evaluated using the Revised University of California, Los Angeles (UCLA) Loneliness Scale. The prevalence of social isolation and loneliness were calculated and multilevel modelling was performed to assess the potential change of these measures before arthroplasty, within a two-year operative-recovery phase and a following two-year follow-up. RESULTS: The sample consisted of 393 people following THA and TKA. The prevalence of social isolation and loneliness changed from 16.9% to 18.8% pre-operative to 21.8% and 18.9% at the final post-operative follow-up respectively. This was not a statistically significant change for either measure (P = 0.15; P = 0.74). There was a significant difference in social isolation at the recovery phase compared to the pre-operative phase (P = 0.01), where people following arthroplasty reported an increase in social isolation (16.9-21.4%). There was no significant difference between the assessment phases in respect to UCLA Loneliness Scale score (P ≥ 0.74). CONCLUSIONS: Given the negative physical and psychological consequences which social isolation and loneliness can have on individuals following THA or TKA, clinicians should be mindful of this health challenge for this population. The reported prevalence of social isolation and loneliness suggests this is an important issue.

Measurements of skeletal muscle mass and power are positively related to a Mediterranean dietary pattern in women.

The age-related loss of skeletal muscle and function are risk factors for osteoporosis and fractures. We found that higher adherence to the Mediterranean diet score was significantly associated with greater fat-free mass and leg explosive power suggesting a role for the Mediterranean Diet in prevention of loss of muscle outcomes. INTRODUCTION: The loss of skeletal muscle mass, strength, and function with age are contributing risk factors for the onset of sarcopenia, frailty, osteoporosis, fractures, and mortality. Nutrition may affect the progression and trajectory of these changes in skeletal muscle but the role of the micronutrient-rich Mediterranean diet (MD) has hardly been investigated in relation to these muscle outcomes. METHODS: We examined associations between the MD score (MDS) and FFM% (fat-free mass / weight × 100), FFMI (fat-free mass/height2), hand grip strength, and leg explosive power (LEP, watts/kg) in a cross-sectional study in 2570 women aged 18-79 years from the TwinsUK study. Measurements of body composition were made using dual-energy X-ray absorptiometry and dietary intake assessed by a food frequency questionnaire. FFM%, FFMI, grip strength, and LEP were compared across quartiles of the MDS after adjustment for covariates, with CRP measured in a subgroup (n = 1658). RESULTS: Higher adherence to the MDS was positively associated with measurements of muscle outcomes, with significant differences of 1.7 % for FFM% and 9.6 % for LEP (P trend <0.001), comparing extreme quartiles of intake, but not with grip strength or CRP concentrations. CONCLUSIONS: For the first time in a northern European population, we have observed significant positive associations between the MDS and FFM% and LEP in healthy women that are potentially clinically relevant, independent of the factors known to influence muscle outcomes. Our findings emphasize the potential role for overall diet quality based on the MD in the prevention of age-related loss of skeletal muscle outcomes.

A higher alkaline dietary load is associated with greater indexes of skeletal muscle mass in women.

UNLABELLED: Conservation of muscle mass is important for fall and fracture prevention but further understanding of the causes of age-related muscle loss is required. This study found a more alkaline diet was positively associated with muscle mass in women suggesting a role for dietary acid-base load in muscle loss. INTRODUCTION: Conservation of skeletal muscle is important for preventing falls and fractures but age-related loss of muscle mass occurs even in healthy individuals. However, the mild metabolic acidosis associated with an acidogenic dietary acid-base load could influence loss of muscle mass. METHODS: We investigated the association between fat-free mass (FFM), percentage FFM (FFM%) and fat-free mass index (FFMI, weight/height²), measured using dual-energy X-ray absorptiometry in 2,689 women aged 18-79 years from the TwinsUK Study, and dietary acid-base load. Body composition was calculated according to quartile of potential renal acid load and adjusted for age, physical activity, misreporting and smoking habit (FFM, FFMI also for fat mass) and additionally with percentage protein. RESULTS: Fat-free mass was positively associated with a more alkalinogenic dietary load (comparing quartile 1 vs 4: FFM 0.79 kg P < 0.001, FFM% 1.06 % <0.001, FFMI 0.24 kg/m² P = 0.002), and with the ratio of fruits and vegetables to potential acidogenic foods. CONCLUSIONS: We observed a small but significant positive association between a more alkaline diet and muscle mass indexes in healthy women that was independent of age, physical activity and protein intake equating to a scale of effect between a fifth and one half of the observed relationship with 10 years of age. Although protein is important for maintenance of muscle mass, eating fruits and vegetables that supply adequate amounts of potassium and magnesium are also relevant. The results suggest a potential role for diet in the prevention of muscle loss.

Sex, military occupation and rank are associated with risk of anterior cruciate ligament injury in tactical-athletes.

INTRODUCTION: Anterior cruciate ligament (ACL) injury is common within the US military and represents a significant loss to readiness. Since recent changes to operational tempo, there has not been an analysis of ACL injury risk. The aim of this retrospective cohort study was to evaluate military occupation, sex, rank and branch of service on ACL injury risk in the US military from 2006 to 2018. METHODS: The Defense Medical Epidemiology Database was queried for the number of US tactical athletes with International Classification of Diseases diagnosis codes 717.83 (old disruption of ACL), 844.2 (sprain of knee cruciate ligament), M23.61 (other spontaneous disruption of ACL) and S83.51 (sprain of ACL of knee) on their initial encounter. Relative risk and χ2 statistics were calculated to assess sex and military occupation effects on ACL injury. A multivariable negative binomial regression model evaluated changes in ACL injury incidence with respect to sex, branch of service and rank. RESULTS: The study period displayed a significant decrease in the ACL injury rate at 0.18 cases per 1000 person-years or relative decrease of 4.08% each year (p<0.001) after averaging over the main and interactive effects of sex, rank and branch of service. The interaction effect of time with sex indicated a steeper decline in the incidence in men as compared with women. The risk of ACL injury by sex was modified by rank. The incidence among military personnel varied by occupation. CONCLUSION: Despite the decline among tactical athletes over time, rates of ACL injury remain much higher than the general US population. Sex, rank, branch of service and military occupation were found to be risk factors for ACL injury. It is critical for policy makers to understand the salient risk factors for ACL injury to guide proactive measures to prevent injury.

Does policy that provides choice in athletic footwear affect musculoskeletal injury risk in US Coast Guard recruits?

INTRODUCTION: Musculoskeletal injuries (MSKIs) are ubiquitous during initial entry military training, with overuse injuries the most common. A common injury mechanism is running, an activity that is integral to US Coast Guard (USCG) training and a requirement for graduation. The purpose of this study was to assess the effects of a policy that allowed for athletic footwear choice on risk of lower quarter MSKI in USCG recruits. METHODS: A retrospective cohort study was performed that included 1230 recruits (1040 men, 190 women) who trained under a policy that allowed self-selection of athletic footwear and 2951 recruits (2329 men, 622 women) who trained under a policy that mandated use of prescribed uniform athletic shoes and served as controls. Demographic data and physical performance were derived from administrative records. Injury data were abstracted from a medical tracking database. Unadjusted risk calculations and multivariable logistic regression assessing the effects of group, age, sex, height, body mass and 2.4 km run times on MSKI were performed. RESULTS: Ankle-foot, leg, knee and lumbopelvic-hip complex injuries were ubiquitous in both groups (experimental: 13.13 per 1000 person-weeks; control: 11.69 per 1000 person-weeks). Group was not a significant factor for any of the injuries assessed in either the unadjusted or adjusted analysis, despite widespread reports of pain (58.6%), perceived injury attribution (15.7%), perceived deleterious effect on performance (25.3%), general dissatisfaction (46.3%) and intended discontinuance of use following graduation (87.7%). CONCLUSION: MSKI continues to be a major source of morbidity in the recruit training population. The policy that allowed USCG recruits to self-select athletic footwear did not decrease or increase the risk of MSKI. While regulations pertaining to footwear choice did not influence injury outcomes, there was general dissatisfaction with the prescribed uniform athletic footwear conveyed by the recruits and widespread reports of discomfort, perceived deleterious effects from wear and intended discontinued use following training completion.

Prescribed footwear and orthoses are not prophylactic in preventing lower extremity injuries in military tactical athletes: a systematic review with meta-analysis.

INTRODUCTION: Military members are exposed to high cumulative physical loads that frequently lead to injury. Prescribed footwear and orthoses have been used to prevent injury. The purpose of this systematic review with meta-analysis was to assess if prescribed prophylactic footwear or foot orthoses reduced the risk of lower extremity injury in military tactical athletes. METHODS: MEDLINE, Embase, Web of Science, Cumulative Index to Nursing and Allied Health Literature, SportDiscus, and Defense Technical Information Center databases were searched for randomised controlled trials published at any time that compared foot orthoses or prescribed footwear (to include shock-absorbing insoles and socks) with a placebo intervention or a no-treatment control. Methodological quality was assessed and the number of injuries, population at risk and duration of the study epoch were extracted and relative risk (RR) calculated. An omnibus meta-analysis was performed assessing all prescribed footwear and orthoses intervention studies, with subgroup analyses conducted on studies with similar interventions (ie, basketball athletic shoes, athletic shoes (prescribed by foot type), foot orthoses, shock-absorbing insoles, socks, tropical combat boots). RESULTS: Of 1673 studies identified, 22 were included. Three of eight studies that employed orthoses demonstrated significantly reduced overuse injuries compared with no-treatment controls (RR range: 0.34-0.68); one study showed neoprene insoles significantly decreased overuse injuries (RR: 0.75). There were no other significant effects in the individual studies and no protective effects observed in the omnibus meta-analysis or in the component subanalyses. CONCLUSIONS: Prescribed footwear and orthoses do not appear to have a prophylactic effect on lower quarter musculoskeletal injuries in military members and cannot be recommended at this time.

The genetic influence on radiographic osteoarthritis is site specific at the hand, hip and knee.

OBJECTIVE: To identify whether a shared genetic influence accounts for the occurrence of OA at different skeletal sites. METHODS: Multivariate modelling of data on prevalent radiographic OA at the hand (DIP, PIP and CMC joints), hip and knee joints assessed in 992 monozygotic and dizygotic female twin participants from the TwinsUK Registry. RESULTS: OA at all the five joint sites was heritable. Genetic influences were strongly correlated among joints in the hand; however, there was little evidence of common genetic pathways to account for the co-occurrence of OA at the hand, hip and knee. CONCLUSIONS: While genetic influences are important in explaining the variation in occurrence of OA at the hand, hip and knee, there is no evidence that common or shared genetic factors determine the occurrence of disease across all these skeletal sites. The findings suggest that there are important aetiological differences in the disease that are site-specific in women. These results have implications for the design of studies examining the genetic basis of OA as well as for strategies aimed at preventing and treating the disease.

Lumbar disc disease shows linkage to chromosome 19 overlapping with a QTL for hand OA.

OBJECTIVE: Cervical and lumbar degenerative disc disease (CDD and LDD, respectively) form part of the spine osteoarthritis (OA) phenotype and are known to be influenced by genetic factors. A genome-wide linkage analysis was performed to identify new chromosomal regions of interest. METHODS: Dizygotic healthy female twin volunteers (n = 348) from the TwinsUK register who had magnetic resonance imaging scans 10 years ago coded for degenerative disease, were identified. Multipoint genome-wide linkage analysis was conducted using 737 highly polymorphic markers of approximate spacing 10 cM. RESULTS: The mean age of the twins was 52 years. Significant linkage peaks (log of the odds (LOD) >3) were identified for LDD at three chromosomal regions. These included chromosome 1 (position 285 cM), chromosome 5 (position 175 cM) and chromosome 19 (position 80 cM). The peak on chromosome 19 had LOD = 4.06, and the empirical p = 6.7x10(-4) confirmed reliability of the linkage signal. It lies close to a linkage peak previously obtained by our group for hand OA. CONCLUSIONS: This genome-wide linkage study of CDD and LDD shows evidence of linkage for LDD on chromosome 19. The region of interest is likely to harbour genes that are common to LDD and hand OA.

Genetic associations in peripheral joint osteoarthritis and spinal degenerative disease: a systematic review.

UNLABELLED: We conducted a systematic review of genetic association studies for osteoarthritis of the peripheral joints (OA) and spinal degenerative disease (SDD). Electronic searches were carried out for any English language article reporting on a gene association study for either OA or SDD published up until the end of 2006. A team of seven reviewers used a standardised template to extract data in duplicate. In all, 90 studies fulfilled our inclusion criteria, reporting a total of 94 significant associations from 83 different genes. We found relatively few instances in which a specific gene-disease association had been analysed by more than one study, and there were 14 cases in which significant associations were replicated in independent studies (at joints associated with the AGC1, ASPN, COL9A2, COL9A3, COL11A2, ESR1, FZRB, HFE, IL1A, IL1RN, PTGS2 and VDR genes). METHOD: logical and reporting problems were widespread, including failure to report full results, missing population details, multiple testing, and over-reliance on subgroup analysis. In summary, the complex phenotypes of OA and SDD may have made it difficult for researchers to focus their efforts. The field is dominated by isolated analyses of disparate potential associations, a problem that is amplified by the frequent analysis of different polymorphisms within individual genes. Flaws in study methodology and interpretation undoubtedly increase the risk of publication bias. Closer adherence to published recommendations (in particular those produced by HuGENet) will help to ensure that future studies are well-designed and build on current understanding, rather than simply adding to the growing bank of potential associations.

Recognition of inflammatory back pain and ankylosing spondylitis in primary care.

OBJECTIVE: The diagnosis of AS is often delayed in primary care. This may partly be due to inability to differentiate inflammatory back pain (IBP) from mechanical. The aim of this study was to assess current practice of general practitioners (GPs) in using clinical, radiological and laboratory investigations to assess patients with IBP. METHODS: A postal questionnaire was sent to all GPs in Norfolk. It was designed to test GPs ability to identify symptoms suggestive of IBP in patients with back pain. It also enquired whether GPs considered other features of SpA. Their perceptions of usefulness of various investigations when considering a diagnosis of AS, management and their unmet needs were recorded. RESULTS: A total of 62% of completed questionnaires were returned. Only 5% of GPs could identify all eight features known to be indicative of IBP, 78% between four and eight and 17% identified less than four features. GPs had a range of views regarding the utility of a positive family history, HLA-B27, use of X-ray and physiotherapy in patients with suspected IBP. GPs awareness of the associated features of SpA was low. There were inconsistencies in the use of diagnostic tests and management of AS. Improving musculoskeletal education in primary care was identified as one of the unmet needs by the majority of GPs. CONCLUSIONS: In a survey of GPs, we identified inconsistencies in their perceptions and approach to the diagnosis and management of AS. Education in primary care and the wider use of diagnostic algorithms may improve early detection and hence outcome of AS.

Migraine and antiphospholipid antibodies: no association found in migraine-discordant monozygotic twins.

Migraine headache (with and without aura) is common in the general population and is known to be influenced by genetic factors with heritability estimates between 34-57%. Antiphospholipid syndrome (APS) is a hypercoagulable state characterized by clinical features including venous and arterial thromboses, pregnancy loss and migraine, and by association with antiphospholipid antibodies (aPL). Numerous small studies have investigated whether aPL are associated with migraine in the general population--with contradictory results. In this study, the question was addressed by studying the prevalence of aPL in members of monozygotic (MZ) twin pairs differing in their migraine status. Such twins provide a unique natural experiment, matched as they are for age, sex and genetic factors, and allow the role of environmental factors, such as aPL, to be determined. Despite 95% power to detect a difference of 0.59 IgG units per litre in anticardiolipin antibody IgG titres, no difference in prevalence of aPL could be detected in migraine-discordant MZ twins.

Twins. Novel uses to study complex traits and genetic diseases.

The challenge faced by research into the genetic basis of complex disease is to identify genes of small relative effect against a background of substantial genetic and environmental variation. This has focused interest on a classical epidemiological design: the study of twins. Through their precise matching for age, the common family environment and background environmental variation, studying diseases in non-identical twins provides a means to enhance the power of conventional strategies to detect genetic influence through linkage and association. The unique matching of identical twins provides researchers with ways to isolate the function of individual genes involved in disease together with approaches to understanding how genes and the environment interact.

Genetics of risk factors for melanoma: an adult twin study of nevi and freckles.

BACKGROUND: We sought by use of an adult twin study to investigate the relative contribution of genetic and environmental effects on the expression of nevi and freckles, which are known risk factors for melanoma, and to determine if age and sun exposure influence the heritability of nevi. DESIGN AND METHODS: Total nevus and freckle counts were conducted on 127 monozygotic twin pairs and 323 dizygotic twin pairs. Intraclass correlations were calculated by use of analysis of variance. Model-fitting analyses were performed to quantify the genetic and environmental components of the variance for nevus and freckle counts. RESULTS: The intraclass correlation for total nevus counts was.83 in monozygotic pairs compared with.51 in dizygotic pairs. Quantitative genetic analyses showed that the contribution of genetic factors on nevi expression varied according to age. For twins less than 45 years old, the additive genetic variance on total nevus count was 36% (95% confidence interval [CI] = 0.8%-63%), with 38% (95% CI = 14%-61%) and 26% (95% CI = 16%-42%) of the remaining variance attributed to common environment and unique environmental effects, respectively. In twins aged 45 years or older, common environmental effects on total nevus count became negligible, with the additive genetic variance increasing to 84% (95% CI = 77%-88%). Body site was also found to affect the heritability estimates for nevus counts, with a statistically significant difference between sun-exposed and sun-protected sites. The polychoric correlation (i.e., the correlation in liability within twins for more than two categories) for total freckle counts was.91 in monozygotic twin pairs compared with.54 in dizygotic twin pairs. Additive genetic effects explained 91% (95% CI = 86%-94%) of the variance in freckle counts. CONCLUSION: The contribution of genetic factors on the variance for total nevus counts increased with age, and sun exposure appears to influence the expression of nevi. The results of this study highlight the need to take into account the age and site of nevus counts for future genetic linkage or association studies in the search for new melanoma genes.

A randomized controlled trial of vitamin D supplementation on preventing postmenopausal bone loss and modifying bone metabolism using identical twin pairs.

Vitamin D supplementation, when given with calcium, has been shown to increase bone mineral density (BMD) and reduce the incidence of hip fracture in elderly subjects. Despite its widespread use, the benefits of vitamin D supplementation in younger women and as a single agent are less clear. We performed a randomized co-twin, placebo-controlled, double-blind trial over 2 years to measure the effect of vitamin D3 supplementation on bone density and bone metabolism in young postmenopausal women. Seventy-nine monozygotic (MZ) twin pairs (mean age, 58.7 years; range, 47-70 years) were recruited. For each twin pair, one was randomized to 800 IU cholecalciferol/day for 2 years and the other was randomized to placebo. BMD was measured at the spine and hip and heel ultrasound at baseline, 12, 18, and 24 months. Samples were collected at 0, 3, and 6 months to measure serum calcium, 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), osteocalcin, and urinary deoxypyridinoline (DPD). In total, 64 pairs completed the study. No differences in baseline characteristics were seen between the groups. At 6 months, the treatment group had an increase in serum vitamin D [mean +/- SEM intrapair difference, 14.1+/-2.4 microg/liter (p < 0.001)]. There were no significant differences in other serum measurements or bone markers at 3 months or 6 months. At 24 months, no significant treatment effect was seen on BMD or calcaneal ultrasound change within pairs. Subanalysis of treatment response by vitamin D receptor (VDR) genotype revealed no significant difference in effect on BMD variables with treatment. On the basis of these results, vitamin D supplementation, on its own, cannot be recommended routinely as an osteoporosis prevention for healthy postmenopausal women with normal vitamin D levels under the age of 70 years.

Genetic contribution to bone metabolism, calcium excretion, and vitamin D and parathyroid hormone regulation.

A classical twin study was performed to assess the relative contribution of genetic and environmental factors to bone metabolism, calcium homeostasis, and the hormones regulating them. It was examined further whether the genetic effect is menopause dependent. The subjects were 2136 adult twins (98.3% female): 384 monozygotic (MZ) and 684 dizygotic (DZ) twin pairs. The intraclass correlations were calculated, and maximum likelihood model fitting was used to estimate genetic and environmental variance components. The intraclass correlations for all of the variables assessed were higher in MZ twin pairs. The heritabilities (95% CIs) obtained from model fitting for hormones regulating bone metabolism and calcium homeostasis were parathyroid hormone (PTH), 60% (54-65%); 25-hydroxyvitamin D [25(OH)D]; 43% (28-57%), 1,25-hydroxyvitamin D [1,25(OH)], 65% (53-74%); and vitamin D binding protein 62% (56-66%). The heritabilities (95% CIs) for markers of bone formation also were assessed; bone-specific alkaline phosphatase (BSAP), 74% (67-80%), and osteocalcin, 29% (14-44%); marker of bone resorption deoxypyridinoline (DPD), 58% (52-64%); and measure of calcium homeostasis 24 h urine calcium, creatinine (Cr), 52% (41-61%). The magnitude of genetic influence differed with menopause for most variables. This study provides evidence for the importance of genetic factors in determining bone resorption and formation, calcium excretion, and the hormones regulating these processes. It shows for the first time a clear genetic effect on bone resorption in premenopausal women and the regulation of PTH, vitamin D metabolism, and calcium excretion. The genes controlling bone hormones and markers are likely to be useful therapeutic and diagnostic targets.

The influence of genetics and environmental factors in the pathogenesis of acne: a twin study of acne in women.

Acne is common and often leads to significant psychologic and physical morbidity. From clinical experience, acne appears to run in families; however, very few studies have investigated the genetic basis of this very common skin disease. A large twin study based on 458 pairs of monozygotic and 1099 pairs of dizygotic twins, all women with a mean age of 46 y was performed to investigate the relative contribution of genetic and environmental factors on the liability to acne. In addition, potential risk factors were assessed in twins with and without acne in a nested cross-sectional design. Fourteen percent of the twins reported a history of acne. Genetic modeling using acne scores showed that 81% (95% confidence interval 73-87%) of the variance of the disease was attributable to additive genetic effects. The remaining 19% was attributed to unique (i.e., unshared) environmental factors. Of the potential risk factors tested in 400 acne twins and 2414 unaffected twins, only apolipoprotein A1 serum levels were significantly lower in acne twins even after adjusting for age and weight. Family history of acne was also significantly associated with an increased risk. No significant differences were found between acne twins and nonacne twins for weight, body mass index, height, birth weight, hair thinning, reproductive factors as well as cholesterol, triglycerides, high-density lipoprotein, and glucose levels. The lower serum levels of apolipoprotein A1 in acne twins were also confirmed when analyzing acne discordant twin pairs. The evidence of a major genetic influence on acne should stimulate the search for potential genes that may lead to new therapeutic approaches.

Genes control the cessation of a woman's reproductive life: a twin study of hysterectomy and age at menopause.

A classical twin study was performed to assess the extent to which genetic factors explain individual differences in age at menopause and (indications for) hysterectomy. It was further examined whether a genetic effect on the timing of the menopause was mediated through a genetic effect on age at menarche. The subjects were 275 monozygotic and 353 dizygotic female twin pairs. Maximum likelihood model fitting was used to estimate genetic and environmental variance components, Kaplan-Meier survival analysis was used to account for censored data, and the Cox proportional hazards model was used to adjust for potential confounders. A model specifying additive genetic and unique environmental factors showed the best fit to the data, yielding a heritability (h2) for age at menopause of 63%. The significance of the genetic effect was confirmed by the survival analysis and was not affected by adjustment for confounders. Both early and late menopause were found to be significantly influenced by genetic factors. Hysterectomy also showed considerable heritability (h2 = 59%), as did its two main indications: fibroids (h2 = 69%) and menorrhagia (h2 = 55%). The genetic contribution to the variance in age at menarche was estimated to be 45%, with the majority (37%) being due to dominant genetic effects. No correlation was found between age at menopause and age at menarche, suggesting different genetic mechanisms. This study provides convincing evidence for the importance of genetic factors in determining natural and surgical menopause. Understanding how genes control the timing of menopause and exploring whether these genes are indirectly associated with disease are important areas for future study.

Analysis of antibody reactivity in the sera of 42 patients with paraproteinaemia.

The clinical expression of disease in patients with conditions in which autoimmunity is thought to contribute to the pathogenesis of disease is the result of an unfortunate combination of predisposing and environmental factors. The presence of autoantibodies showing a variety of antigen specificities in sera from many of these patients has been closely correlated with particular spectra of organ involvement or tissue destruction. Their precise role in the disease process is as yet unclear. Sera from patients with paraproteinaemia also often contain autoantibodies to a variety of cell components, although symptoms of autoimmune disease are rarely found in this group of individuals. In this study of 42 sera from patients with paraproteinaemia we have confirmed the presence of autoantibodies in 33% (13/42) of samples. Amongst the autoantibodies detected were those to human neutrophils (3), U1RNP (8) and cardiolipin (4). In five sera, the immunoglobulin class of autoantibody did not correlate with that of the monoclonal band. This study extends previous reports of the repertoire of autoantibodies present in sera from patients with paraproteinaemia.

An identical twin pair discordant for rheumatoid arthritis and ankylosing spondylitis.

Both rheumatoid arthritis (RA) and ankylosing spondylitis (AS) have an increased familial occurrence and each disease is associated with the inheritance of specific HLA antigens. We report a pair of identical twin brothers with discordant disease phenotypes: one developed AS at the age of 26, and the other developed RA at the age of 55. The twins possessed both of the disease susceptibility antigens HLA B27 and DR4. Differences in the twins' environmental exposure are discussed.