Renal Response Outcomes of the EuroLupus and National Institutes of Health Cyclophosphamide Dosing Regimens in Childhood-Onset Proliferative Lupus Nephritis.

OBJECTIVE: We compared clinical characteristics and renal response in patients with childhood-onset proliferative lupus nephritis (LN) treated with the EuroLupus versus National Institutes of Health (NIH) cyclophosphamide (CYC) regimen. METHODS: A retrospective cohort study was conducted at 11 pediatric centers in North America that reported using both CYC regimens. Data were extracted from the electronic medical record at baseline and 3, 6, and 12 months after treatment initiation with CYC. To evaluate the adjusted association between CYC regimen (EuroLupus vs NIH) and renal response over time, generalized estimating equations with a logit link were used. An interaction between time and CYC regimen was included, and a contrast between CYC regimens at 12 months was used to evaluate the primary outcome. RESULTS: One hundred forty-five patients (58 EuroLupus, 87 NIH) were included. EuroLupus patients were on average older at the start of current CYC therapy, had longer disease duration, and more commonly had relapsed or refractory LN compared with the NIH group. After multivariable adjustment, there was no significant association between CYC regimen and achieving complete renal response at 12 months (odds ratio [OR] of response for the EuroLupus regimen, reference NIH regimen: 0.76; 95% confidence interval [CI] 0.29-1.98). There was also no significant association between CYC regimen and achieving at least a partial renal response at 12 months (OR 1.35, 95% CI 0.57-3.19). CONCLUSION: Our study failed to demonstrate a benefit of the NIH regimen over the EuroLupus CYC regimen in childhood-onset proliferative LN. However, future prospective outcome studies are needed.

From Microcytosis to Macrodiagnosis.

A 12-year-old Hispanic girl presented with fatigue, lightheadedness, and intermittent headaches. She was depressed and appeared pale to her mother. Her examination was unremarkable except for palpebral conjunctival pallor and was otherwise noncontributory. She had a profound hypoproliferative microcytic anemia with low iron level, low transferrin saturation, and a normal ferritin level. The patient experienced improvement in clinical symptoms following transfusion of packed red blood cells and oral iron therapy. At follow-up 2 months later, she presented with similar symptoms and persistent microcytic anemia with low iron levels. Her ferritin level was increased along with markedly elevated C-reactive protein and erythrocyte sedimentation rate. An oral iron challenge demonstrated lack of absorption, and hepcidin level was also significantly elevated. Thorough gastrointestinal and rheumatologic evaluations were performed to search for a source of inflammation. Key components of the patient's social history supplemented by serology, radiographic, and pathologic findings ultimately cinched an unexpected diagnosis.

Adaptations of Interferon Regulatory Factor 3 with Transition from Terrestrial to Aquatic Life.

Interferon regulatory factor 3 (IRF3) and IRF7 are closely related IRF members and the major factors for the induction of interferons, a key component in vertebrate innate immunity. However, there is limited knowledge regarding the evolution and adaptation of those IRFs to the environments. Two unique motifs in IRF3 and 7 were identified. One motif, GASSL, is highly conserved throughout the evolution of IRF3 and 7 and located in the signal response domain. Another motif, DPHK, is in the DNA-binding domain. The ancestral protein of IRF3 and 7 seemed to possess the DPHK motif. In the ray-finned fish lineage, while the DPHK is maintained in IRF7, the motif in IRF3 is changed to NPHK with a D → N amino acid substitution. The D → N substitution are also found in amphibian IRF3 but not in amphibian IRF7. Terrestrial animals such as reptiles and mammals predominantly use DPHK sequences in both IRF3 and 7. However, the D → N substitution in IRF3 DPHK is again found in cetaceans such as whales and dolphins as well as in marsupials. These observations suggest that the D → N substitutions in the IRF3 DPHK motif is likely to be associated with vertebrate's adaptations to aquatic environments and other environmental changes.

Adverse pregnancy outcomes in adolescents and young women with systemic lupus erythematosus: a national estimate.

BACKGROUND: Pregnant women with systemic lupus erythematosus (SLE) have increased risk of adverse outcomes including disease flare, spontaneous abortion, preeclampsia/eclampsia, premature birth and maternal death. However, pregnancy outcomes among adolescents and young women with SLE have not been well-explored. Our objective was to compare risk of adverse pregnancy outcomes in adolescents and young women with SLE to risk among peers without SLE. METHODS: We studied the 2000-2011 Nationwide Inpatient Sample (NIS) of the Healthcare Cost and Utilization Project (HCUP) to estimate the prevalence of adverse pregnancy outcomes in women with SLE aged ≤ 21 years at time of delivery. Outcomes were compared to peers without SLE by using multivariate logistic regression to calculate odds ratios and risk differences. Additionally, differences in length of stay and total charges per hospitalization were described. RESULTS: There were 8,791,391 unique pregnancies, of which 4002 occurred in young women with SLE. After adjustment for age, race, insurance type and quartile of median income based on patient ZIP code individuals with SLE had increased odds of pre-eclampsia/eclampsia (OR 3.2, 95% CI 2.3-4.6), maternal death (OR 80, 95% CI 10-604), preterm birth (OR 2.7, 95% CI 2-3.7), spontaneous abortion (OR 5.1, 95% CI 2.8-9.6), and induced abortion (OR 30, 95% CI 14-63). The increase in risk among women with SLE was greatest for preterm birth (RD 11%, 95% CI 6-16), pre-eclampsia/eclampsia (RD 9%, 95% CI 5-13), and spontaneous abortion (RD 4%, 95% CI 0.9-6). Risk difference for induced abortion was 2% with 95% CI 0.6-4, while the difference in risk for maternal death did not reach statistical significance (RD 0.4, 95% CI -0.4-1). CONCLUSIONS: Adolescents and young women with SLE experience increased risk of adverse, pregnancy-specific outcomes as compared to their peers, including pre-eclampsia/eclampsia, maternal death, preterm birth, spontaneous abortion, and induced abortion. Additionally, length of stay and total charges for hospitalization are increased.