A Review of Complement Activation in SLE Weinstein, Arthur; Alexander, Roberta V.; Zack, Debra J.
Current rheumatology reports,
02/2021, Volume:
23, Issue:
3
Journal Article
Peer reviewed
Open access
Purpose of Review
Complement activation is a key event in the pathogenesis of tissue inflammation and injury in systemic lupus erythematosus (SLE). This review is aimed at comparing the usefulness of ...measurement of complement proteins in serum/plasma (C3, C4) to complement activation (split) products in plasma and on circulating blood cells for SLE diagnosis, disease monitoring, and prognosis.
Recent Findings
Complement split products, C3dg, iC3b, and C4d, are elevated in SLE, and C3dg/C3 and iC3b/C3 ratios correlate with active SLE. C4d also is higher in patients with lupus nephritis. An elevated level of the alternative pathway split product, Bb, in early lupus pregnancy is a predictor of adverse outcomes in SLE patients with antiphospholipid antibodies. Elevated levels of cell-bound complement activation products (CB-CAPs), namely, B cell-bound C4d (BC4d) and erythrocyte-bound C4d (EC4d), within a multiparameter assay panel, may predict transition to SLE more than other lupus biomarkers. EC4d better correlates with lupus disease activity than low plasma complement levels. Elevated platelet-bound C4d (PC4d) correlates with thrombosis in SLE. Both EC4d and PC4d are increased in primary and secondary anti-phospholipid syndrome, and anti-beta2glycoproteinI antibodies may directly activate the complement system.
Summary
Abnormal levels of plasma complement split products and CB-CAPs support complement activation as an important pathogenetic mechanism in SLE and the antiphospholipid syndromes. These tests show promise for the diagnosis of SLE and monitoring of disease activity.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Naomi Rothfield was truly a pied piper of lupus. She had an abiding interest in the characterization and clinical significance of antinuclear antibodies and anti-DNA antibodies in the serum of ...systemic lupus erythematosus (SLE) patients. She described the use of serum complement in SLE diagnosis and the association of inherited complement deficiencies with SLE. Under her leadership, numerous professionals focused their clinical and research activities to benefit lupus patients. Naomi was also instrumental in establishing a lupus group to assist lupus patients, which became one of the founding chapters of the Lupus Foundation of America.
Purpose To assess the effectiveness and safety of a multifocal intraocular lens (IOL) with +2.5 diopter (D) additional power compared with a monofocal IOL. Setting Fifteen sites in the United States. ...Design Prospective randomized patient- and observer-masked clinical trial. Methods Randomized patients received multifocal or monofocal IOLs bilaterally. Visual acuity (33 cm, 40 cm, 53 cm, 60 cm, 4 m) was measured; safety was assessed through adverse event rates. Patient-reported visual outcomes were evaluated using the Visual Tasks questionnaire. The frequency and severity of visual disturbances were evaluated using the Assessment of Photic Phenomena and Lens EffectS questionnaire. Results The multifocal IOL (n = 155) provided better corrected distance visual acuity at 53 cm than the monofocal IOL (n = 165) (0.322 versus 0.512 logMAR; between-group difference, −0.190 logMAR; P < .0001) and 40 cm but not at 4 m. Ocular adverse event rates were less than 3.84% in both groups. Serious adverse event rates were comparable between the 2 IOL types. Patients with multifocal IOLs reported less difficulty with near tasks (with and without correction) and intermediate tasks (without correction). Difficulty with extended-intermediate and distance tasks was similar between groups. The most frequently reported self-rated severe phenomena were halos, starbursts, and glare. Most patients (monofocal ≥72%; multifocal ≥73%) reported never experiencing blurred, distorted, or double vision. Conclusions The +2.5 D multifocal IOL provided better vision at 40 cm and 53 cm and similar vision at 4 m compared with the monofocal IOL. Safety profiles and visual phenomena were comparable between groups.
Summary Advocacy for Lyme disease has become an increasingly important part of an antiscience movement that denies both the viral cause of AIDS and the benefits of vaccines and that supports unproven ...(sometimes dangerous) alternative medical treatments. Some activists portray Lyme disease, a geographically limited tick-borne infection, as a disease that is insidious, ubiquitous, difficult to diagnose, and almost incurable; they also propose that the disease causes mainly non-specific symptoms that can be treated only with long-term antibiotics and other unorthodox and unvalidated treatments. Similar to other antiscience groups, these advocates have created a pseudoscientific and alternative selection of practitioners, research, and publications and have coordinated public protests, accused opponents of both corruption and conspiracy, and spurred legislative efforts to subvert evidence-based medicine and peer-reviewed science. The relations and actions of some activists, medical practitioners, and commercial bodies involved in Lyme disease advocacy pose a threat to public health.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Objective
To describe a new systemic lupus erythematosus (SLE) responder index (SRI) based on a belimumab phase II SLE trial and demonstrate its potential utility in SLE clinical trials.
Methods
Data ...from a randomized, double‐blind, placebo‐controlled study in 449 patients of 3 doses of belimumab (1, 4, 10 mg/kg) or placebo plus standard of care therapy (SOC) over a 56‐week period were analyzed. The Safety of Estrogens in Lupus Erythematosus: National Assessment (SELENA) version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and British Isles Lupus Assessment Group (BILAG) SLE disease activity instruments, the Short Form 36 health survey, and biomarker analyses were used to create a novel SRI. Response to treatment in a subset of 321 serologically active SLE patients (antinuclear antibodies ≥1:80 and/or anti–double‐stranded DNA antibodies ≥30 IU/ml) at baseline was retrospectively evaluated using the SRI.
Results
SRI response is defined as 1) a ≥4‐point reduction in SELENA–SLEDAI score, 2) no new BILAG A or no more than 1 new BILAG B domain score, and 3) no deterioration from baseline in the physician's global assessment by ≥0.3 points. In serologically active patients, the addition of belimumab to SOC resulted in a response in 46% of patients at week 52 compared with 29% of the placebo patients (P = 0.006). SRI responses were independent of baseline autoantibody subtype.
Conclusion
This evidence‐based evaluation of a large randomized, placebo‐controlled trial in SLE resulted in the ability to define a robust responder index based on improvement in disease activity without worsening the overall condition or the development of significant disease activity in new organ systems.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Gout in the axial skeleton Konatalapalli, Rukmini M; Demarco, Paul J; Jelinek, James S ...
Journal of rheumatology,
03/2009, Volume:
36, Issue:
3
Journal Article
Peer reviewed
Open access
Gout typically affects the peripheral joints of the appendicular skeleton and rarely involves the axial joints. The literature on axial gout is limited to case reports and case series. This ...preliminary study was conducted to identify the frequency and characteristics of axial gout.
Six hundred thirty medical records with ICD codes 274.0, 274.82, and 274.9 for peripheral gout were reviewed. Ninety-two patients had clinical or crystal-proven gout, of which 64 had prior computed tomography (CT) images of the spine performed for various medical reasons. These CT images were reviewed for features of axial gout, which include vertebral erosions mainly at the discovertebral junction and the facet joints, deposits of tophi, and erosions in the vertebral body, epidural space, ligamentum flavum and pars interarticularis.
Nine of the 64 patients had radiographic changes suggestive of axial gout. Lumbar vertebrae were most commonly involved, with facet joint erosions being the most common finding. Isolated involvement of the sacroiliac joints was seen in 2 patients. Axial gout had been diagnosed clinically in only one patient.
Radiologic changes of axial gout were more common than recognized clinically, with a frequency of 14%. Since not all patients had CT images, it is possible that the frequency of axial involvement was even greater. A prospective study is needed to further define this process.
PDF
