Determination of serum free light chains as a marker of systemic lupus flare.

INTRODUCTION: The aim of this study was to explore the usefulness of the determination of free light chains (FLC) in serum as a biomarker of flare in patients with systemic lupus erythematosus (SLE) and to analyze the differences in their discriminatory capacity with complement C3 and C4. METHODS: This was a prospective cohort study. The definition of flare was based on the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Flare Index. The discriminatory capacity of FLC and C3 and C4 levels was compared using receiver operating characteristic (ROC) curves and the area under the curve (AUC). RESULTS: Forty-six patients were enrolled. Patients with SLE flare showed significantly lower C3 (p = 0.025) and C4 levels (p = 0.028), as well as a higher concentration of lambda light chains (λ-LC) (p = 0.028) compared with the non-flare group. λ-LC, as opposed to kappa light chains and total light chains, demonstrated a discriminatory capacity for detecting the presence of SLE flare (AUC 0.781), with 100% sensitivity, 65% specificity, and 69.6% of patients correctly classified for a cutoff point of ≥ 19.5 mg/L. Complement C3 and C4 also showed a high discriminatory capacity for SLE flare (AUC 0.804 and 0.837, respectively). Comparing λ-LC, C3, and C4, the last one demonstrates better discriminatory capacity for SLE flare with the highest AUC (0.837; 95% CI 0.663-1.000). CONCLUSIONS: λ-LC have good discriminatory capacity for SLE flare and could be useful as a biomarker of SLE exacerbation.Key Points• The usefulness of free light chains as a biomarker could be compared with complement.• Lambda free light chains have good discriminatory capacity for SLE flare.• Free light chains are a promising marker of SLE activity.

Prevalence of Celiac Disease in a Long-term Study of a Spanish At-genetic-risk Cohort From the General Population.

OBJECTIVES: To perform long-term celiac disease (CD) screening in an HLA-DQ2 (+) cohort from the general population and to assess the influence of risk genotypes on its development. METHODS: In 2004, an HLA-DQ2 (+) cohort was selected. After the first CD screening at age 2 to 3 years, we performed a follow-up screening 8 to 10 years later. Antitransglutaminase 2 antibodies were determined using a rapid test kit. Results were confirmed by serum IgA antitransglutaminase 2 and IgA endomysial antibody determination. CD diagnosis was carried out by intestinal biopsies. Four HLA-DQ2 genotypic groups were used: G1: DQ2.5/DQ2.5 (G1A) or DQ2.5/ DQ2.2 (G1B); G2: DQ2.2/DQ7.5 (DQ2.5 trans); G3: DQ2.5/ X; G4: DQ2.2/X. RESULTS: CD prevalence after 10 years of follow-up was 5.8% (95% confidence interval 3.8-8.7). One of every 3 HLA-DQ2(+) children carried at least 1 haplotype DQ2.2 or DQ7. The homozygous genotype DQ2.5/DQ2.5 and the HLA-DQ2.5 trans genotype increased CD risk 4- and 3-fold, respectively. The homozygous genotype DQ2.5/ DQ2.2 did not increase the CD risk. Children carrying G1 or G2 genotypes were diagnosed with CD earlier and more frequently during the follow-up compare with those carrying G3 or G4 genotypes. Approximately 81% of children with spontaneous antibody negativization after the first screening maintained negative antibodies. CONCLUSIONS: A repeated screening of at-risk children during their follow-up allowed us to diagnose new CD cases. In our cohort, HLA- DQ2.5 trans genotype conferred a higher risk in the development of CD than HLA- DQ2.5/DQ2.2. The majority of children with potential CD and CD autoimmunity at 10 years of age remained healthy.

Prevalence and Natural History of Celiac Disease in a Cohort of At-risk Children.

OBJECTIVES: To assess the prevalence and clinical presentation of celiac disease (CD) in a cohort of children with HLA-DQ2 positive and evaluate the risk factors in the development of CD. METHODS: Between July 2004 and July 2005, parents of all healthy full-term newborns in our hospital were invited to participate. HLA-DQ2 was tested in blood sample of the umbilical cord. A point of contact serological test was performed on children between 2 and 3 years of age. Positive results were confirmed by serum anti-transglutaminase 2 and endomysial antibodies. Children with high autoantibody titers underwent an intestinal biopsy. Children of the cohort diagnosed with CD before the screening study were included. Sex, mode of delivery, breast-feeding duration, and age of gluten introduction were studied. RESULTS: Of 1291 children, 362 were HLA-DQ2 positive and 262 participated in the study. CD was diagnosed in 4.1% (95% confidence interval (CI) 1.9-6.3). In the whole cohort, 60% had gastrointestinal symptoms, 7% poor weight gain, and 33% were asymptomatic. Five children with potential CD and 6 with CD autoimmunity became negative (42.3%) and are still negative after 5 to 7 years. Female sex was at-risk factor odds ratio 5.7 (95% CI 1.5-20.9), whereas breast-feeding during gluten introduction had a protective effect odds ratio 0.1 (95% CI 0.01-0.8). CONCLUSIONS: Prevalence of CD in this cohort was 4%, half of whom had digestive symptoms. Because a high proportion of children showed a spontaneous disappearance of antibodies, prevalence studies of CD in young children should be based on intestinal damage so as not to overestimate results.