most commonly in hands, wrists, and knees

including homozygous deficiencies of early components of complement

Estradiol binds to receptors on T and B lymphocytes, increasing activation and survival of those cells, especially autoreactive subsets, thus favoring prolonged immune responses

B cells not only present antigens, but they also secrete IL-6 and IL-10, which promote autoreactive B-cell survival (as does estrogen)

The activated innate immune system interacts with various subsets of the B and T cells of adaptive immunity. SLE peripheral B cells have increased numbers of naïve activated B cells and double-negative B cells (DN2: CD27–CD11c+T-BET+CXCR5–), which are precursors of autoantibody-secreting cells. Both subsets have abnormal epigenetic modifications with more open chromatin than normal B cells and thus are subject to hyperactivation via their B-cell receptors, Toll-like receptor 7 (TLR7), and cytokines such as IL-21. Therefore, SLE B cells are poised to react to their environment with increased autoantibody secretion. Central B cells (germinal center, follicular B cells) also produce autoantibodies. DN2 and isotype-switched memory B cells differentiate into both short-lived (in periphery) and long-lived (in bone marrow) plasma cells that secrete autoantibodies and are elevated in patients with active SLE. B cells not only present antigens, but they also secrete IL-6 and IL-10, which promote autoreactive B-cell survival (as does estrogen). Some B and T lymphocyte subsets have altered metabolism (abnormal mitochondrial electron transport, membrane potential, and oxidative stress), increased glucose utilization, increased pyruvate production, activation of mechanistic target of rapamycin (mTOR), and increased autophagy. Helper T cells are easily activated and driven into either differentiation, activation, or apoptosis. In SLE patients, after peptides bind the T-cell receptor (TCR), T-cell signaling is abnormal, beginning with complexing of TCR with the common chain FcRγ rather than the usual CD3ζ. This results in abnormal elevations of phosphorylated Syk, the P13K/mTORC pathway, CaMKIV, PP2A, and calcineurin, with resultant increased calcium influx. Rho-associated protein kinases (ROCK) pathways are also elevated, probably via cytokine receptors, with increases in STAT3 and therefore in IL-17. The net result is underproduction of IL-2 (needed for survival of T lymphocytes and for generation of regulatory T cells) and elevation of IL-17. These changes push the adaptive immune system toward generation of helper T cells (TH1, Tfh, TH17) and away from downregulating regulatory T cells. Several of these B- and T-cell pathways are targets of therapeutic interventions in current clinical trials.

Consider the addition of oral glucocorticoids

Diffuse glomerular disease; can be further subdivided into

Focal glomerular disease

Class II or V lupus nephritis confirmed on renal biopsy

Class III or IV lupus nephritis confirmed on renal biopsy

Entry criterion

niebla tóxica

• Gastroenteritis, cólera y otras enfermedades infecciosas transmitidas por alimentos y agua, provocadas por la contaminación derivada de la afectación de los suministros de agua potable y de las redes de tratamiento de aguas residuales, tras inundaciones y otras catástrofes medioambientales.

Enfermedades cardiovasculares, cerebrovasculares y respiratorias