Molecular profiling of kidney compartments from serial biopsies differentiate treatment responders from non-responders in lupus nephritis.

The immune pathways that define treatment response and non-response in lupus nephritis (LN) are unknown. To characterize these intra-kidney pathways, transcriptomic analysis was done on protocol kidney biopsies obtained at flare (initial biopsy (Bx1)) and after treatment (second biopsy (Bx2)) in 58 patients with LN. Glomeruli and tubulointerstitial compartments were isolated using laser microdissection. RNA was extracted and analyzed by nanostring technology with transcript expression from clinically complete responders, partial responders and non-responders compared at Bx1 and Bx2 and to the healthy controls. Top transcripts that differentiate clinically complete responders from non-responders were validated at the protein level by confocal microscopy and urine ELISA. At Bx1, cluster analysis determined that glomerular integrin, neutrophil, chemokines/cytokines and tubulointerstitial chemokines, T cell and leukocyte adhesion genes were able to differentiate non-responders from clinically complete responders. At Bx2, glomerular monocyte, extracellular matrix, and interferon, and tubulointerstitial interferon, complement, and T cell transcripts differentiated non-responders from clinically complete responders. Protein analysis identified several protein products of overexpressed glomerular and tubulointerstitial transcripts at LN flare, recapitulating top transcript findings. Urine complement component 5a and fibronectin-1 protein levels reflected complement and fibronectin expression at flare and after treatment. Thus, transcript analysis of serial LN kidney biopsies demonstrated how gene expression in the kidney changes with clinically successful and unsuccessful therapy. Hence, these insights into the molecular landscape of response and non-response may help align LN management with the pathogenesis of kidney injury.

Remission of lupus nephritis: the trajectory of histological response in successfully treated patients.

OBJECTIVE: This study investigated changes in kidney histology over time in patients with lupus nephritis (LN) undergoing immunosuppressive treatment. METHODS: Patients with proliferative±membranous LN were studied. After a diagnostic kidney biopsy (Bx1), patients had protocol biopsy 2 (Bx2) at 9 (6-15) months and protocol biopsy 3 (Bx3) at 42 (28-67) months. Kidney histological activity and chronicity indices (AI, CI) were measured. RESULTS: AI declined in a biphasic fashion, falling rapidly between Bx1 and Bx2 and then more slowly between Bx2 and Bx3. Patients were divided into those who achieved histological remission, defined as an AI=0 at Bx3 (group 1), and those with persistent histological activity (AI >0) at Bx3 (group 2). The early decline in AI was 1.6 times greater (95% CI 1.30, 1.91) in group 1 than group 2 (p=0.01). Between Bx2 and Bx3, the AI decline was 2.19-fold greater (95% CI 2.09, 2.29) in group 1 versus group 2 (p=7.34×10-5). Individual histological components of the AI resolved at different rates. Inflammatory lesions like glomerular crescents, karyorrhexis and necrosis mostly resolved by Bx2, whereas endocapillary hypercellularity, subendothelial hyaline deposits and interstitial inflammation resolved slowly, accounting for residual histological activity at biopsy 3 in group 2. In contrast, CI increased rapidly, by 0.15 units/month between Bx1 and Bx2, then plateaued. There were no differences in the rate of accumulation of chronic damage between group 1 and group 2. The increase in CI was significantly related to the severity of glomerular crescents (p=0.044), subendothelial hyaline deposits (p=0.002) and interstitial inflammation (p=0.015) at Bx1. CONCLUSIONS: LN histological activity takes months to years to resolve, providing a rationale for the need of long-term, well-tolerated maintenance immunosuppression. Despite responding, LN kidneys accrue chronic damage early during treatment. This finding provides an explanation for the association of chronic progressive kidney disease with recurrent episodes of LN.

Carcinoma neuroendocrino de la piel: Carcinoma de células de Merkel. Revisión de la Literatura, a propósito de un caso / Neuroendocrine skin carcinoma: Merkel cell carcinoma. Review of literature, about a case

El carcinoma de células de Merkel, también llamado carcinoma neuroendocrino de la piel, es un tipo de cáncer de piel muy poco frecuente que generalmente aparece como un nódulo de color carne o rojo azulado, más frecuentemente en región facial, cabeza y cuello. El carcinoma de células de Merkel se desarrolla principalmente en personas mayores ya que la exposición al sol a largo plazo o un sistema inmunitario débil pueden aumentar el riesgo de desarrollarlo. Las células de Merkel se encuentran en la base de la capa más externa de la piel (epidermis) y están conectadas a las terminaciones nerviosas que son responsables del sentido del tacto. Tiende a crecer rápido y diseminarse a otras partes del cuerpo. Por tanto, las opciones de tratamiento para el carcinoma de células de Merkel dependen de si el cáncer se ha diseminado más allá de la piel

Merkel cell carcinoma, also called neuroendocrine skin of the skin, is a very rare type of skin cancer that generally appears as a bluish meat or red color nodule, more frequently in the facial, head and neck region. Merkel cell carcinoma develops mainly in older people since long -term exposure or a weak immune system can increase the risk of developing it. Merkel cells are at the base of the outermost layer of the skin (epidermis) and are connected to nerve endings that are responsible for the sense of touch. It tends to grow quickly and spread to other parts of the body. Therefore, the treatment options for Merkel cell carcinoma depend on whether cancer has spread beyond the skin