Antiphospholipid antibodies (aPL) can induce fetal loss in experimental animal models. Human studies did find hypocomplementemia associated to pregnancy complications in patients with Antiphospholipid Syndrome (APS), but these results are not unanimously confirmed. We have then performed a multicenter study to identify if preconception decreased C3 and/or C4 levels could be considered a risk factor for adverse pregnancy outcome (APO) in APS and aPL carriers pregnancies.
We performed a multicenter study including 503 pregnancies from 11 Italian and 1 Russian Centers. Data in women with APS and asymptomatic carriers with persistently positive aPL and preconception complement levels were available for 260 pregnancies.
93 (36%) of all pregnancies had low levels of preconception C3 (51, 55, %) or C4 (13, 14%) or both (29, 31%). 167 (64%) pregnancies had normal complement levels. In pregnancies with low preconception C3/C4, a significantly higher prevalence of pregnancy losses was observed (p=0.008). A subgroup analysis focusing on triple aPL positive patients found out that preconception low C3 and/or C4 levels was associated with an increased rate of pregnancy loss (p=0.05) as shown in Table 1.
Our findings confirm that decreased complement levels before pregnancy are associated with increased risk of APO. Pregnancy losses has been seen only in women with triple aPL positivity, indeed single or double positivity does not show this trend. Complement levels are cheap and easy to be measured therefore they could represent a useful aid to identify patients at increased risk of pregnancy loss.
Patients with Systemic lupus erythematosus (SLE) still have increased mortality and risk of cancer than general population. In this study, we investigated the mortality and risk of cancer of SLE patients.
This study was conducted in Hanyang BAE lupus cohort from 1998 to 2015. Mortality and malignancy data were linked from the Korean National Statistics Office and the Korea Central Incidence Database. The Standardized Mortality Ratio (SMR) and Standardized Incidence Ratio (SIR) was estimated by dividing the observed number of events by the expected number of events of age- and sex- matched general population of matched year.
In 1284 patients, total 71 deaths were observed. The most common cause of death was SLE (52.1%) followed by infection (18.3%), cerebrovascular disease (8.5%) and suicide (7.0%). The total age- and sex- adjusted SMR was 3.4 [95% CI (Confidential Interval) 2.6-4.1]. SMR in patients younger than 20, aged 20-39, aged 40-59 and over 60 were was 12.2 (95% CI 0-26.0), 9.8, 3.7, and 1.0, respectively.
Malignancy data were available in 1,020 patients. Fifty-five solid tumor (24 thyroid cancers, 5 colorectal cancers, 4 breast cancers, 4 cervical cancers, et al) and 5 hematologic malignancies was developed. The total age- and sex- adjusted SIR was 1.1 (95% CI 0.8-1.4).
Patients with SLE had higher risk of mortality than general population and the younger patients had the higher risk of mortality. The leading cause of death was SLE itself followed by infection and cerebrovascular disease. The risk for cancer SLE patients was similar with that of general population.
Antiphospholipid antibody (aPL) is commonly present in SLE patients. We tried to identify the impact of persistent presence of aPL on target achievement in a real-world SLE cohort.
Records of our Peking University First Hospital SLE cohort from 2007 to 2019 were retrospectively reviewed. Patients were divided into SLE with persistent aPL and no-persistent aPL group in general, and 3 subgroups were further separated from the former, namely SLE with APS, SLE with at least two aPLs positivity, and SLE with persistent aPL yet delayed HCQ use. The attainment of LLDAS or remission, and relevant components in each patient group were analyzed by Cox proportional hazards model in propensity-score matched and unmatched cohorts.
626 SLE patients with 9415 visits were included in the study. Time to first LLDAS achievement was significantly longer in those with overlapping APS. After balancing confounders, overlapping APS and persistent aPL yet delayed HCQ initiation were associated with 61%, 77% lower probability of reaching LLDAS, and 48%, 84% lower probability of reaching clinical RONT. While the hazardous impact of persistent presence of aPL and at least two aPLs positivity was limited to serologic normalization. Both persistent aPL and its three subgroups hampered immunosuppressant discontinuation with HRs 0.82-0.51. Moreover, the harm of delayed HCQ initiation in the first 6 months was robust throughout all the relevant components.
Persistent aPL hampered SLE patients from reaching normal serology, while overlapping APS and delayed HCQ initiation in the first 6 months further exacerbated the difficulty of reaching remission and LLDAS.