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Журнал "Почки" №1 (19) 2017

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Ïîãëÿä íà ïðîáëåìó / Looking at the Ðroblem<br />

markers to distinguish these two forms, considering<br />

that it is not always possible to do this using clinical<br />

information alone, as this enables the most appropriate<br />

treatment and management to be selected. The work of<br />

Beck et al. presented a large step forward in the diagnosis<br />

of MN, detecting the circulating antigens phospholipase<br />

A2 receptor (PLA2R), IgG4, and thrombospondin<br />

type 1 domain-containing 7A (THSD7A) in<br />

the sera of primary MN patients [23]. However, there<br />

is still the strong need for further markers that can be<br />

used to stratify primary MN patients, given that the<br />

aforementioned antigens only account for approximately<br />

75 % of primary MN patients. Here, Smith et<br />

al. employed MALDI-MSI to FFPE tissue of 20 patients<br />

to evaluate the capability of this technology to<br />

detect alterations in the tissue proteome of primary<br />

and secondary MN patients and represented the first<br />

example of MALDI-MSI being applied to FFPE renal<br />

biopsies for this purpose. The positive results obtained<br />

with this proteomic approach facilitated the detection<br />

of a number of signals that could differentiate the different<br />

forms of iMN that were positive to PLA2R or<br />

IgG4 as well as distinguish primary from secondary<br />

MN. In particular, MALDI-MSI was able to generate<br />

molecular signatures of primary and secondary MN,<br />

with one particular signal (m/z 1459), identified as<br />

Serine/threonine-protein kinase MRCK gamma, being<br />

over-expressed in the glomeruli of primary MN<br />

patients with respect to secondary MN. Furthermore,<br />

this proteomic approach detected a number of signals<br />

that could differentiate the different forms of iMN that<br />

were positive to PLA2R or IgG4 as well as a further set<br />

of signals (m/z 1094, 1116, 1381 and 1459) that distinguish<br />

these patients from those who were ne gative to<br />

both. Although this study is only in the initial phase,<br />

the preliminary results are encouraging and the line of<br />

work holds a fair degree of promise. Following verification<br />

on a larger cohort of patients, the signals detected<br />

here could potentially represent future proteomic<br />

markers of iMN [24].<br />

All these studies show vast potential and represent<br />

the value of employing modern proteomic techniques<br />

for diagnostic purposes, particularly in CKD. It is<br />

hoped that this already strong platform will encourage<br />

further, more in-depth, studies that could eventually<br />

reveal new specific and sensitive biomarkers that could<br />

be used for the diagnosis, prognosis, and management<br />

of renal disease. Renal diseases, as a very specific entity,<br />

have been more widely investigated and understood<br />

than ever before during recent decades. However, given<br />

the ever increasing worldwide incidence of CKD,<br />

in addition to advancements in analytical instrumentation,<br />

it is both important, and possible, to obtain much<br />

more molecular information than was ever possible.<br />

Understanding the molecular nature of this disease will<br />

open new horizons in its diagnosis management strategies.<br />

A vast amount of information on this topic is accessible<br />

on the OMICS international website which includes<br />

open-access journals and other various information<br />

(https://www.omicsonline.org/) as well as the CKD<br />

database (http://www.padb.org/ckddb/).<br />

Conflicts of interests: not declared.<br />

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Òîì 6, ¹ 1, <strong>2017</strong><br />

www.mif-ua.com, http://kidneys.zaslavsky.com.ua 29

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