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 />
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