Cohesion and Organization Patterns Among Family Members Coping with Rheumatoid Arthritis

1999 ◽  
Vol 29 (3) ◽  
pp. 79-95 ◽  
Author(s):  
Deborah M. Whitley ◽  
Elizabeth Beck ◽  
Rodney Rutkowski
Keyword(s):  
Rheumatoid Arthritis ◽  
Family Members

scholarly journals Distinct Roles of Vav Family Members in Adaptive and Innate Immune Models of Arthritis

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 695
Author(s):  
Javier Conde ◽  
Isabel Fernández-Pisonero ◽  
Myriam Cuadrado ◽  
Antonio Abad ◽  
Javier Robles-Valero ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Family Members ◽  
Experimental Models ◽  
Innate Immune ◽  
Main Role ◽  
Zymosan A ◽  
Proliferation And Differentiation ◽  
Signal Transduction Proteins ◽  
Selection Of

Genetic evidence suggests that three members of the VAV family (VAV1, VAV2 and VAV3) of signal transduction proteins could play important roles in rheumatoid arthritis. However, it is not known currently whether the inhibition of these proteins protects against this disease and, if so, the number of family members that must be eliminated to get a therapeutic impact. To address this issue, we have used a collection of single and compound Vav family knockout mice in experimental models for antigen-dependent (methylated bovine serum albumin injections) and neutrophil-dependent (Zymosan A injections) rheumatoid arthritis in mice. We show here that the specific elimination of Vav1 is sufficient to block the development of antigen-induced arthritis. This protection is likely associated with the roles of this Vav family member in the development and selection of immature T cells within the thymus as well as in the subsequent proliferation and differentiation of effector T cells. By contrast, we have found that depletion of Vav2 reduces the number of neutrophils present in the joints of Zymosan A-treated mice. Despite this, the elimination of Vav2 does not protect against the joint degeneration triggered by this experimental model. These findings indicate that Vav1 is the most important pharmacological target within this family, although its main role is limited to the protection against antigen-induced rheumatoid arthritis. They also indicate that the three Vav family proteins do not play redundant roles in these pathobiological processes.

Antiphospholipid Syndrome: Clinical Characteristics of Patients and Affected Family Members From Multiplex Families.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2972-2972
Author(s):  
Thomas L. Ortel ◽  
Fatih Cagri Sarikaya ◽  
Ahmet Alptekin ◽  
Karen E. Hansen ◽  
Robert A.S. Roubey ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Antiphospholipid Syndrome ◽  
Clinical Manifestation ◽  
Clinical Characteristics ◽  
Family Members ◽  
Autoimmune Disorders ◽  
Antiphospholipid Antibody ◽  
Type I ◽  
Thromboembolic Events ◽  
Common Clinical Manifestation

Abstract Abstract 2972 Poster Board II-950 Background: Antiphospholipid syndrome (APS) is characterized by venous and/or arterial thromboembolic events, recurrent fetal loss, and persistently elevated antiphospholipid antibody (aPL) levels. Familial clustering of individuals with elevated aPL levels occurs, and up to 37% of patients with APS have one or more relatives with at least one clinical feature of APS. Individuals with elevated aPL levels or APS are also frequently identified in families with other autoimmune (AI) disorders, such as lupus or rheumatoid arthritis. Individuals with different autoimmune disorders appear to share common susceptibility loci, suggesting that a common set of susceptibility genes may contribute to clinically distinct autoimmune disorders. To investigate the heritability of APS, we are enrolling patients with APS who have one or more family members affected by APS (multiplex APS) or by other, non-APS, autoimmune disorders (multiplex AI). This study summarizes clinical characteristics of probands and family members enrolled to date in these two groups. Methods: Probands meeting clinical and laboratory criteria for APS (Miyakis, et al. J.Thromb.Haemost, 2006;4: 295-306) who had at least one clinically affected relative positive for either APS or another autoimmune disorder (e.g., lupus, rheumatoid arthritis) were recruited and enrolled into the study. A detailed personal and family history was obtained and relevant family members were also approached to participate in the study. Blood specimens were collected for genetic, serologic, and coagulation testing. Results: Review of more than 200 potential participants identified 13 probands with multiplex APS families and 49 with multiplex AI families. Probands from both groups more frequently had primary rather than secondary APS, and thromboembolic events were the most common clinical manifestation. Catastrophic APS was reported in 1 multiplex APS proband and 4 multiplex AI probands. Proband characteristics are summarized in the Table. In the multiplex APS families, 1 to 3 family members had APS, and the most common clinical manifestation was thromboembolism. In addition, 8 multiplex APS families also had one or more family members who were affected with other autoimmune disorders, most commonly lupus and rheumatoid arthritis. In the multiplex AI families, 1 to 8 family members were affected by a variety of autoimmune disorders, including lupus, Hashimoto's disease, Sjögren's syndrome, rheumatoid arthritis, myasthenia gravis, type I diabetes mellitus, and other diseases. Affected family members most commonly included siblings and/or parents of the probands. Conclusions: In the participants enrolled to date, probands with APS who belonged to multiplex APS or multiplex AI families most commonly had primary APS, and thromboembolic complications were the most common clinical manifestation. Families that were multiplex AI were more common than families that included more than one family member affected with APS, and families that were multiplex APS frequently included members that had other autoimmune disorders. Disclosures: No relevant conflicts of interest to declare.

The psychosocial status of the family members of rheumatoid arthritis patients in Korea

2016 ◽  
Vol 36 (5) ◽  
pp. 719-724 ◽  
Author(s):  
Sang Wan Chung ◽  
You Jung Ha ◽  
Eun Ha Kang ◽  
Yun Jong Lee ◽  
Yeong Wook Song
Keyword(s):  
Rheumatoid Arthritis ◽  
Family Members ◽  
Psychosocial Status ◽  
The Family

scholarly journals OP0118 DECIPHERING THE ANTI-PROTEIN-ARGININE DEIMINASE (PAD) RESPONSE IDENTIFIES PAD1 AND PAD6 AS NOVEL AUTOANTIGENS IN RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 78-79
Author(s):  
L. Martinez-Prat ◽  
M. A. Aure ◽  
C. Bentow ◽  
D. Lucia ◽  
M. Lopez-Hoyos ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Principal Component Analysis ◽  
Family Members ◽  
Principal Component ◽  
Arginine Deiminase ◽  
In Vitro Diagnostics ◽  
Positive Fraction ◽  
Protein Arginine Deiminase ◽  
Inova Diagnostics

Background:Protein-arginine deiminase (PAD) 4 enzymes play a central role in the pathogenesis of rheumatoid arthritis (RA) and represents an antigenic target. Among the five known family members (PAD1, PAD2, PAD3, PAD4 and PAD6), only PAD2, PAD3 and PAD4 have been described to have autoantigenic properties. Furtheremore, very little is known on the the isotype usage of these autoantibodies. Understanding the molecular basis of the anti-PAD antibody reponse has the potential to open novel approaches for precision medicine in RA.Objectives:The objectives of this study were to screen for the presence of antibodies to the five PAD family members and to evaluate the isotype usage of the anti-PAD4 response in RA.Methods:First, we developed a panel for the detection of anti-PAD IgG based on a particle-based multi-analyte technology (PMAT), that utilized paramagnetic particles coupled with the different human recombinant PAD proteins (PAD1, PAD2, PAD3, PAD4 and PAD6) and anti-human IgG conjugate. This panel was used to test sera from RA patients (n=33) and non-RA controls (n=36). The controls were comprised of apparently healthy individuals (n=10), and patients with infectious diseases (n=10), systemic lupus erythematosus (n=7), systemic sclerosis (n=9) and Sjogren’s syndrome (n=1). Next, the PAD4-coupled beads were tested with anti-human IgM, IgA and IgG conjugates on an extended cohort of RA patients (n=62) and the same non-RA controls.Results:All five anti-PAD IgG (Figure 1) demonstrated the ability to discriminate between RA patients and controls. At greater than 90% specificity, anti-PAD4 IgG, followed by anti-PAD3 IgG, showed the best diagnostic performance. Significantly higher levels of the five antibodies were observed in RAvs.controls (p-values of 0.0041, <0.0001, 0.0014, 0.0039, and 0.0140 for anti-PAD1, 2, 3, 4 and 6, respectively). Significant correlation was observed between all the antibodies, with the highest between anti-PAD1 and anti-PAD4 (Spearman´srho=0.87,p<0.0001) and the lowest between anti-PAD4 and anti-PAD2 (Spearman’srho=0.38,p=0.0015) and anti-PAD4 and anti-PAD6 (Spearman’srho=0.38,p=0.0011). While principal component analysis (PCA) (Figure 2) showed an association between all anti-PAD antibodies, there was further discrimination that displayed closer association between anti-PAD1, 3 and 4 on one hand, and between anti-PAD2 and 6. For the extended testing of anti-PAD4 with IgG, IgA and IgM, all three isotypes were identified in the sera of RA patients. Higher levels of the three isotypes were observed in RA patients with erosive disease when compared with the patients without erosion, but this association was only significant for anti-PAD4 IgA (p=0.0086).Figure 1.Receiver operating characteristics (ROC) analysis of the discrimination between rheumatoid arthritis (RA) and controls of IgG to protein-arginine deiminase (PAD) 1, PAD2, PAD3, PAD4 and PAD6. The area under the curve (AUC) values are shown in brackets for each biomarker.Abbreviations:TPF: true positive fraction; FPF: false positive fractionFigure 2.Two dimensional principal component analysis (PCA) plot of the anti-PAD levels in RA patients (n=33) and controls (n=36). Anti-PAD1, 3 and 4 have the main contribution to PC1, which explains 51.7% of the variance, and anti-PAD2 and 6 to PC2, that represents 20.8% of it.Abbreviations:PC: principal componentConclusion:Our study is the first to describe PAD1 and PAD6 as novel antigenic targets in RA and to demostrate that the anti-PAD4 B-cell immune response uses all three isotypes (IgG, IgA and IgM). The strong and significant association between anti-PAD4 IgA and joint erosion is of particular clinical relevance.Disclosure of Interests:Laura Martinez-Prat Employee of: I am an employee of Inova Diagnostics, an in vitro diagnostics company., Mary Ann Aure Employee of: I am an employee of Inova Diagnostics, an in vitro diagnostics company., Chelsea Bentow Employee of: I am an employee of Inova Diagnostics, an in vitro diagnostics company., David Lucia Employee of: I am an employee of Inova Diagnostics, an in vitro diagnostics company., Marcos Lopez-Hoyos Consultant of: Inova Diagnostics, an in vitro diagnostics company., Michael Mahler Employee of: I am an employee of Inova Diagnostics, an in vitro diagnostics company.

Mutations of the cystic fibrosis gene in patients with bronchiectasis associated with rheumatoid arthritis

2010 ◽  
Vol 70 (4) ◽  
pp. 653-659 ◽  
Author(s):  
Xavier Puéchal ◽  
Thierry Bienvenu ◽  
Emmanuelle Génin ◽  
Jean-Marie Berthelot ◽  
Jean Sibilia ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cystic Fibrosis ◽  
Genetic Factors ◽  
Genetic Defect ◽  
Family Members ◽  
Cystic Fibrosis Gene ◽  
Degree Relative ◽  
Family Based ◽  
Important Marker

ObjectivesIn cystic fibrosis, mutations of the CFTR gene lead to diffuse bronchiectasis (DB). DB is also associated with other diseases including rheumatoid arthritis (RA) in which the role of genetic factors in the predisposition to DB remains unclear.MethodsA family-based association study was carried out to determine whether the frequency of CFTR mutations was higher in patients with RA-associated DB and to determine whether a causal relationship could be established between the variant and the disease by evaluating its cosegregation with DB within families. Families of probands with RA-DB were included if one first-degree relative had RA and/or DB. The controls comprised healthy subjects requesting genetic counselling because their partner had cystic fibrosis.ResultsThe frequency of CFTR mutations was higher in family members with RA-DB or DB only than in unaffected relatives (p<0.005 for each comparison) and in unrelated healthy controls (p<0.001 for each comparison) but not in family members with RA only. CFTR mutations were more frequent in family members with RA-DB than in those with RA only (OR 5.30, 95% CI 2.48 to 11.33; p<5×10−5). They cosegregated with RA-DB in the families (sib-TDT=10.82, p=0.005).ConclusionsRA-DB should be added to the list of phenotypes in which CFTR mutations are pathogenic. CFTR mutation is the first genetic defect linked to an extra-articular feature of RA to be described. CFTR mutations in patients with RA appear to be an important marker of the risk of associated DB, which has been linked to a less favourable prognosis.

A Prospective Study of the Development of Inflammatory Arthritis in the Family Members of Indigenous North American People With Rheumatoid Arthritis

2019 ◽  
Vol 71 (9) ◽  
pp. 1494-1503 ◽  
Author(s):  
Stacy Tanner ◽  
Brenden Dufault ◽  
Irene Smolik ◽  
Xiaobo Meng ◽  
Vidyanand Anaparti ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Prospective Study ◽  
North American ◽  
Inflammatory Arthritis ◽  
Family Members ◽  
American People ◽  
The Family ◽  
A Prospective Study

scholarly journals Exome Sequencing in a Family with Chronic Lymphocytic Leukemia, Mantle Cell Lymphoma and Autoimmune Disease Uncovers Potential Germline Risk-Alleles

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5629-5629
Author(s):  
Martha J Glenn ◽  
Rosalie G Waller ◽  
Nicola J Camp
Keyword(s):  
Rheumatoid Arthritis ◽  
Quality Control ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Genetic Factors ◽  
Cell Lymphoma ◽  
Family Members ◽  
Lymphocytic Leukemia ◽  
Risk Alleles ◽  
Mantle Cell

Abstract We identified a Caucasian family with dense distribution of B-cell non-Hodgkin lymphoma (NHL) and autoimmune disease (Figure 1). Within the family, three siblings and their mother have B-cell NHL (three with chronic lymphocytic leukemia [CLL]; one with mantle cell lymphoma [MCL]), and four family members have autoimmune diseases (rheumatoid arthritis or multiple sclerosis). In addition, two family members have melanoma. To investigate the genetic factors involved in B-cell NHL in this family, we exome sequenced nine individuals, including two unaffected spouses as technical-artifact controls. Following best-practice guidelines, we performed joint variant calling, including an additional 135 European 1000Genome exomes as a set of background controls. Figure 1 Figure 1. After variant quality control, a total of 676,137 sequence variants were identified. We also performed individual genotype quality control based on a minimum read depth of 10 and genotype quality of 40, resulting in 554,690 variants. For our initial prioritization, we required that variants be: absent in the spouse controls, have minor allele frequency (MAF) ≤ 0.05 in the 1000Genome exomes, and be shared by all four B-cell NHL cases. This resulted in 73 variants of potential interest. Of the 73 variants, seven were predicted to be damaging by either PROVEAN or SIFT, two by both algorithms and by PolyPhen2. These two potentially damaging variants reside in the genes CCDC144A and RRS1. The gene CCDC144A is located at chromosome 17p11.2, a known breakpoint region of the 17p deletion often seen in CLL tumor cells. The variant identified in this gene was rare (MAF = 0.001 in the NHLBI Exome Sequencing Project [ESP]) and was also seen in two additional family members (one with rheumatoid arthritis; a second with rheumatoid arthritis and melanoma). The gene RRS1 is located at chromosome 8q13.1, and has been shown to be important for proper chromosomal organization during mitosis. The variant identified in this gene was relatively rare (MAF = 0.041 in ESP) and was seen in the same, two additional family members. Of the remaining five variants predicted damaging by only one algorithm, of interest were two variants in the SGK223 gene on chromosome 8p23.1. SGK223 is a kinase and a component in the BCR-ABL1 signaling network that is present in most chronic myelogenous leukemia cases and a quarter of adult acute lymphoblastic leukemia cases. Both of the variants in SGK223 were also seen in three additional family members (one with rheumatoid arthritis; a second with rheumatoid arthritis and melanoma; a third with melanoma). In addition to prioritization by predicted function of coding variants, we explored the 73 variants for overlap with findings from published germ-line investigations of B-cell NHL. This identified one variant in the ACOXL gene at chromosome 2q13. The variant is relatively rare (MAF = 0.017 in dbSNP) and lies in the same gene and intron (17,016 base pairs upstream) as rs13401811, the associated SNP (p = 2.08 x 10-18) reported in a genomewide association study (GWAS) for CLL. Our ongoing analyses and prioritization of the variants in this extraordinary family reveal overlap with signals coming from GWAS studies and suggest some potentially damaging variants in genes not previously implicated in NHL. The potential risk-alleles identified in our preliminary findings could shed new light about the genes and genetic factors involved in NHL. Disclosures No relevant conflicts of interest to declare.

Employment and Household Work Disability in Women with Rheumatoid Arthritis

1992 ◽  
Vol 23 (1) ◽  
pp. 44-51 ◽  
Author(s):  
Saralynn H. Allaire
Keyword(s):  
Rheumatoid Arthritis ◽  
Work Performance ◽  
Family Members ◽  
Household Work ◽  
Personal Factors ◽  
Rehabilitation Professionals ◽  
Relative Contribution ◽  
Personal Variables ◽  
Financial Need ◽  
The Impact

This study examines the impact of rheumatoid arthritis (RA) on the employment and household work roles of women with families, as well as the relative contribution of health, family and personal factors to role accomplishment. The participation of other family members and paid help in household work, and methods of coping with role impairment were also assessed. 142 women with RA and 58 female neighbors completed questionnaires which assessed role performance and health, family, and personal variables. Employment status was measured by number of hours spent; household work performance in six activity areas was measured by amount of time spent and proportion done. The results are that women with mild RA reported little role disability, while those with more severe RA reported substantial disability. The family members of women with more severe RA spend considerably more time doing household work than their peers, and little paid household help is used, even by those with higher incomes. Financial need was most highly associated with employment, while functional status was the factor most highly associated with household Work performance. The results suggest that rehabilitation professionals should address both employment and household work management issues with women who have disabilities.

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