| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T308 |
0-162 |
Sentence |
denotes |
Systemic lupus erythematosus is a multisystemic autoimmune chronic inflammatory disorder that mainly involves joints, mucosae, skin, and endothelial vessels [90]. |
| T309 |
163-252 |
Sentence |
denotes |
For a long time, HCQ has played a marginal role in the overall management of the disease. |
| T310 |
253-408 |
Sentence |
denotes |
Since the 90s, the first evidence of HCQ effectiveness in controlling lupus erythematosus manifestations allowed its employment as a first-line medicament. |
| T311 |
409-558 |
Sentence |
denotes |
Although it was not recommended in single therapy, the immunomodulating properties of HCQ seem to play an important role in the disease pathogenesis. |
| T312 |
559-691 |
Sentence |
denotes |
It is associated with a decrement of exacerbation events, as well as protective effects towards vascular and thrombotic events [85]. |
| T313 |
692-939 |
Sentence |
denotes |
Indeed, a 24-week randomized, double-blind placebo-controlled trial demonstrated that the discontinuing of HCQ treatment (100–400 mg/kg/day for at least six months) increased the risk of exacerbations by 2.5 times in patients with quiescent lupus. |
| T314 |
940-1076 |
Sentence |
denotes |
People who interrupted the therapy exhibited constitutional symptoms of the disease, as well as skin rashes, arthritis, and ulcers [83]. |
| T315 |
1077-1292 |
Sentence |
denotes |
A long-term randomized study evaluated the withdrawal effects of HCQ on quiescent lupus erythematosus patients, revealing that a reduction by up to 57% is associated with HCQ maintaining treatment (272 mg/day) [84]. |
| T316 |
1293-1414 |
Sentence |
denotes |
A case-control study was carried out in order to define the role of HCQ in the survival of individuals affected by lupus. |
| T317 |
1415-1592 |
Sentence |
denotes |
The positive correlation between HCQ and survival led to the consideration of this drug as a great therapeutic option at the proper dose (6.5 mg/kg/bw) in lupus management [85]. |
| T318 |
1593-1822 |
Sentence |
denotes |
If these clinical trials demonstrated the advantages of keeping up the therapy with HCQ in preventing disease exacerbations, doubts persisted about the efficacy of this treatment in the control of more severe clinical forms [83]. |
| T319 |
1823-1997 |
Sentence |
denotes |
As the important role of the imbalance between immune cell populations, several preclinical and clinical studies have evaluated the role of HCQ in restoring this equilibrium. |
| T320 |
1998-2254 |
Sentence |
denotes |
In particular, elevated levels of effector lymphocyte T (Th17) that mediate the autoimmune answer and decreased levels of regulatory lymphocyte T (Treg) that guarantees the immune homeostasis, may be observed in autoimmune diseases, in particular in lupus. |
| T321 |
2255-2347 |
Sentence |
denotes |
Lately, autophagy had risen among the emerging strategies to reestablish the immune balance. |
| T322 |
2348-2509 |
Sentence |
denotes |
As HCQ is a well-known autophagy inhibitor, An, N. et al. [86] evaluated the influence of HCQ intake (100 mg/kg/day) in MRL/lpr mice with the lupus-like disease. |
| T323 |
2510-2660 |
Sentence |
denotes |
After four weeks of treatment, HCQ clearly restored the immune balance, by both inhibiting Th17 response and enhancing Treg immunosuppressive effects. |
| T324 |
2661-2943 |
Sentence |
denotes |
The levels of autoantibodies and the expression of inflammatory cytokines, mainly in Th17 cells, were remarkably lowered, due to the inhibition of the activated autophagy, as demonstrated by the increase of autophagic flux marker expression in Th17 and Treg, compared with controls. |
| T325 |
2944-3128 |
Sentence |
denotes |
This randomized trial further evidenced that HCQ treatment also remarkably attenuated kidney inflammation, by limiting the migration of lymphoplasmacytic cells into renal tissues [86]. |
| T326 |
3129-3280 |
Sentence |
denotes |
Preclinical outcomes have been confirmed by a prospective cohort study, involving 41 patients with a diagnosis of lupus treated with 400 mg/day of HCQ. |
| T327 |
3281-3631 |
Sentence |
denotes |
Dysregulated cytokine and autoantibody production, deriving from high autoreactivity that characterizes lupus disease, has been restored by two months of HCQ administration, demonstrating its ability in modulating inflammatory response, with normalized complement activity and reduced levels of pro-inflammatory cytokines, mainly IL-6 and TNF-α [87]. |
| T328 |
3632-3924 |
Sentence |
denotes |
In a multiethnic US cohort on 35 lupus patients, HCQ treatment resulted in significant clinical benefits towards disease progression, probably due to the inhibition of toll-like receptor activation, resulting in down-regulation of IFN-α, which plays a pivotal role in lupus pathogenesis [88]. |