ABSTRACT
OBJECTIVE: To develop a model to predict RA outcome based on biochemical variables and single nucleotide polymorphisms (SNPs). METHODS: We collected baseline data from RA patients. SNP genotyping was performed using an oligonucleotide microarray. Remission and severe disability were investigated as outcomes of the study. Logistic regression models and receiver operating characteristic (ROC) curves were used to determine sensitivity (S), specificity (Sp) and likelihood ratio (LR). RESULTS: Six hundred and thirty-two patients (375 in the study and 257 in the validation) were included. Twenty-two out of 152, and 19 out of 208 patients had an HAQ > 2. The model obtained to predict disability included levels of the anti-cyclic citrullinated peptide (anti-CCP) antibodies, ESR and SNP rs2070874 in the IL-4 gene. Homozygous and heterozygous carriers of the IL-4 33T allele had a decreased risk of severe disability. The discriminative power had an area under the curve (AUC) of 0.792 (95% CI 0.694, 0.889), with S 41%, Sp 95% and LR +7.6. Twenty-one out of 268 and 17 out of 211 patients were in remission in the study and validation cohorts, respectively. The model included absence of anti-CCP antibodies and the SNP rs2476601 on the PTPN22 gene. Homozygous and heterozygous carriers of the PTPN22 1858T allele had a decreased probability of remission. The discriminative power had an AUC of 0.842 (95% CI 0.756, 0.928), with S 76%, Sp 86% and LR + 5.4. Predictive ability was confirmed on the validation cohort. CONCLUSIONS: We have developed two models based on laboratory variables that are associated with relevant outcomes for RA patients at disease onset.
Subject(s)
Arthritis, Rheumatoid/diagnosis , Polymorphism, Single Nucleotide , Adult , Aged , Arthritis, Rheumatoid/genetics , Arthritis, Rheumatoid/physiopathology , Arthritis, Rheumatoid/therapy , Autoantibodies/blood , Biomarkers/blood , Disability Evaluation , Epidemiologic Methods , Female , Genetic Markers , Genotype , Humans , Interleukin-4/genetics , Male , Middle Aged , Oligonucleotide Array Sequence Analysis/methods , Peptides, Cyclic/immunology , Prognosis , Remission InductionABSTRACT
We report two pediatric patients with unusual, aggressive initial manifestation of antiphospholipid antibody syndrome secondary to systemic lupus erythematosus. The first patient, a 13-year-old girl, presented with bilateral amaurosis and ischemic cerebral lesions. The second, another 13-year-old girl, presented with cerebral venous sinus thrombosis and membranous glomerulonephritis. Both patients improve after treatment with anticoagulants and immunosuppressive drugs, two therapies that are aimed at modulating the immune response or towards preventing thromboembolic events. However, there is no consensus regarding the duration and intensity of oral anticoagulation in children with antiphospholipid antibody syndrome.
