Benefits of anticitrullinated peptides examination in rheumatoid arthritis

Background: Anti‑citrullinated peptides antibodies (ACPA) are specific for rheumatoid arthritis and have been implicated in disease pathogenesis. ACPA examination is a new component of ACR/EULAR 2010 classification criteria for rheumatoid arthritis. ACPA positivity predicts a more erosive disease course with severe joint damage and extra‑articular manifestations.Objectives: To evaluate the benefits of ACPA examination in patients with early undifferentiated arthritis and patients with rheumatoid arthritis.Methods: We examined patients with arthritis and tested them for ACPA positivity. In every individual patient we evaluated if ACPA examination was necessary to establish the diagnosis of rheumatoid arthritis, or to change treatment, or if the diagnosis could have been established without ACPA examination (ACR/EULAR 2010 classification criteria was met without ACPA scoring).Results and Conclusions: The study was placed in Slovak Republic. We examined 833 patients with arthritis. There were 43 patients, or 62% of a subgroup of 69 who were ACPA positive whose ACPA examination was not needed—ACR/EULAR criteria was met without ACPA scoring. This number represents 5.1% of the total number examined. There were 15 patients, or 22% of the subgroup and 1.8% of the total whose diagnosis was revised to rheumatoid arthritis due to ACPA positivity—ACR/EULAR criteria were met solely with ACPA scoring. There were 11 patients (16% and 1.3%) whose medication was changed due to ACPA positivity. ACPA examination is useful in 3.1% of all examined patients. When we correlate data on ACPA positive patients, 38% of the patients profit from ACPA examinations. Considering the relatively low price of ACPA testing, this examination should not be excluded.Keywords: ACR/EULAR 2010 classification criteria, anti‑citrullinated peptides antibodies, rheumatoid arthriti

Early Diagnosing and Treatment of Rheumatoid Arthritis, Benefits of Anti-Citrullinated Peptides Examination

Background: Anti-citrullinated peptides antibodies (ACPA) are specific for rheumatoid arthritis and have been implicated in disease pathogenesis. ACPA examination is a new component of ACR/EULAR 2010 classification criteria for rheumatoid arthritis. ACPA positivity predicts a more erosive disease course with severe joint damage and extra-articular manifestations. Objectives: To evaluate the benefits of ACPA examination in patients with early undifferentiated arthritis and patients with rheumatoid arthritis. Methods: We examined patients with arthritis and tested them for ACPA positivity. In every individual patient we evaluated if ACPA examination was necessary to establish the diagnosis of rheumatoid arthritis, or to change treatment, or if the diagnosis could have been established without ACPA examination (ACR/EULAR 2010 classification criteria was met without ACPA scoring). Results and Conclusions: We examined 833 patients with arthritis. There were 43 patients, or 62 % of a subgroup of 69 who were ACPA positive whose ACPA examination was not needed - ACR/EULAR criteria was met without ACPA scoring. This number represents 5.1 % of the total number examined. There were 15 patients, or 22 % of the subgroup and 1.8 % of the total whose diagnosis was revised to rheumatoid arthritis due to ACPA positivity - ACR/EULAR criteria was met solely with ACPA scoring. There were 11 patients (16 % and 1.3 %) whose medication was changed due to ACPA positivity. ACPA examination is useful in 3,1 % of all examined patients. When we correlate data on ACPA positive patients, 38 % of the patients profit from ACPA examinations. Considering the relatively low price of ACPA testing, this examination should not be excluded

Deficiency in parvalbumin, but not in calbindin D-28k upregulates mitochondrial volume and decreases smooth endoplasmic reticulum surface selectively in a peripheral, subplasmalemmal region in the soma of Purkinje cells

The Ca²⁺-binding proteins parvalbumin (PV) and calbindin D-28k (CB) are key players in the intracellular Ca²⁺-buffering in specific cells including neurons and have profound effects on spatiotemporal aspects of Ca²⁺ transients. The previously observed increase in mitochondrial volume density in fast-twitch muscle of PV−/− mice is viewed as a specific compensation mechanism to maintain Ca²⁺ homeostasis. Since cerebellar Purkinje cells (PC) are characterized by high expression levels of the Ca²⁺ buffers PV and CB, the question was raised, whether homeostatic mechanisms are induced in PC lacking these buffers. Mitochondrial volume density, i.e. relative mitochondrial mass was increased by 40% in the soma of PV−/− PC. Upregulation of mitochondrial volume density was not homogenous throughout the soma, but was selectively restricted to a peripheral region of 1.5 μm width underneath the plasma membrane. Accompanied was a decreased surface of subplasmalemmal smooth endoplasmic reticulum (sPL-sER) in a shell of 0.5 μm thickness underneath the plasma membrane. These alterations were specific for the absence of the “slow-onset” buffer PV, since in CB−/− mice neither changes in peripheral mitochondria nor in sPL-sER were observed. This implicates that the morphological alterations are aimed to specifically substitute the function of the slow buffer PV. We propose a novel concept that homeostatic mechanisms of components involved in Ca²⁺ homeostasis do not always occur at the level of similar or closely related molecules. Rather the cell attempts to restore spatiotemporal aspects of Ca²⁺ signals prevailing in the undisturbed (wildtype) situation by subtly fine tuning existing components involved in the regulation of Ca²⁺ fluxes