{"id":1086,"date":"2016-12-08T22:49:30","date_gmt":"2016-12-08T21:49:30","guid":{"rendered":"http:\/\/www.newslab.sk\/2016\/12\/08\/monoklonove-gamapatie-laboratorne-vysetrenia-v-diagnostike-a-monitorovani\/"},"modified":"2017-10-04T14:40:55","modified_gmt":"2017-10-04T12:40:55","slug":"monoclonal-gammopathies-laboratory-tests-in-diagnosis-and-monitoring","status":"publish","type":"post","link":"https:\/\/www.newslab.sk\/en\/monoclonal-gammopathies-laboratory-tests-in-diagnosis-and-monitoring\/","title":{"rendered":"Monoclonal gammopathies \u2013 laboratory tests in diagnosis and monitoring"},"content":{"rendered":"
*All tables, charts, graphs and pictures that are featured in this article can be found in the .pdf \r\nattachment at the end of the paper. <\/span><\/strong><\/pre>\n
 <\/p>\n
\u00da<\/strong>vod<\/strong><\/p>\n
Klasifik\u00e1cia zalo\u017een\u00e1 na biologickom potenci\u00e1li patologick\u00e9ho bunkov\u00e9ho klonu tradi\u010dne rozli\u0161uje mal\u00edgne a ben\u00edgne MG (tabu\u013eka 1). Premal\u00edgne \u0161t\u00e1dium ochorenia, tzv. monoklonov\u00e1 gamapatia nejasn\u00e9ho v\u00fdznamu (monoclonal gammopathy of undetermined significance \u2013 MGUS), sa prejavuje len patolo- gick\u00fdm laborat\u00f3rnym n\u00e1lezom M-prote\u00ednu. Rozdelenie MG na asymptomatick\u00e9 a symptomatick\u00e9 je zalo\u017een\u00e9 na pr\u00edtomnosti zn\u00e1mok org\u00e1nov\u00e9ho po\u0161kodenia, ktor\u00e9 sa deteguj\u00fa najm\u00e4 pomocou \u00a0laborat\u00f3rnych n\u00e1lezov. Diagnostick\u00e9 krit\u00e9ri\u00e1 mnohopo\u010detn\u00e9ho myel\u00f3mu, najv\u00fdznamnej\u0161ej MG, sumarizuje tabu\u013eka 2.<\/p>\n
Laborat\u00f3rna diagnostika MG zah\u0155\u0148a \u0161irok\u00e9 spektrum hematologick\u00fdch, biochemick\u00fdch, imunologick\u00fdch, cytotologick\u00fdch a genetick\u00fdch vy\u0161etren\u00ed.
\n
\nCie\u013eom laborat\u00f3rnej diagnostiky je:<\/strong><\/p>\n
    \n
  1. potvrdenie \u00a0klon\u00e1lnej expanzie plazmocytov<\/li>\n
  2. d\u00f4kaz ak\u00e9hoko\u013evek org\u00e1nov\u00e9ho po\u0161kodenia<\/li>\n
  3. vy\u0161etrenie prognostick\u00fdch \u00a0markerov \u2013 pri vo\u013ebe terapie a pri ur\u010den\u00ed dlhodobej progn\u00f3zy<\/li>\n
  4. monitorovanie progresie ochorenia alebo \u00fa\u010dinku lie\u010dby<\/li>\n<\/ol>\n
     <\/p>\n
    Detekcia monoklonov\u00e9ho prote\u00ednu<\/strong><\/p>\n
      \n
    1. Celkov\u00e9 bielkoviny v s\u00e9re:<\/strong> hyperprotein\u00e9mia nad 90 g\/l m\u00f4\u017ee by\u0165 prvou zn\u00e1mkou mo\u017enej MG.<\/li>\n
    2. \u00a0Imunoglobul\u00edny kvantitat\u00edvne:<\/strong> stanovuje sa sum\u00e1rna koncentr\u00e1cia\u00a0polyklonov\u00fdch \u00a0aj monoklonov\u00fdch imunoglobul\u00ednov (M-Ig). Pri vysok\u00fdch\u00a0koncentr\u00e1ci\u00e1ch M-Ig je nutn\u00e9 s\u00e9rum riedi\u0165, \u010do vedie k nadhodnoteniu\u00a0stanovenia, najm\u00e4 pri IgM. U v\u00e4\u010d\u0161iny pacientov so symptomatick\u00fdm\u00a0MM je pr\u00edtomn\u00e1 supresia polyklonov\u00fdch imunoglobul\u00ednov.<\/li>\n
    3. Elektrofor\u00e9za s\u00e9rov\u00fdch bielkov\u00edn umo\u017e\u0148uje detekciu M-gradientu od ve\u013ekosti cca 1,0 g\/l. Gradient je naj\u010dastej\u0161ie tvoren\u00fd kompletnou molekulou M-Ig alebo len jej stavebn\u00fdmi s\u00fa\u010das\u0165ami \u2013 \u013eahk\u00fdmi re\u0165azcami.<\/li>\n<\/ol>\n
      Denzitometrick\u00fd odhad ve\u013ekosti M-prote\u00ednu<\/strong> nekoreluje v\u017edy s kvantitou celkov\u00fdch Ig (r\u00f4zna afinita farbiva k monoklonovej bielkovine, nadhodnotenie celkov\u00fdch Ig).
      \nPr\u00ed\u010diny falo\u0161nej negativity:<\/em> mal\u00e9 gradienty spl\u00fdvaj\u00face s beta-a alfa2-globul\u00ednmi, atypick\u00e9 dif\u00fazne gradienty v d\u00f4sledku tvorby dim\u00e9rov alebo polym\u00e9rov IgM a IgA alebo agreg\u00e1tov IgG, tvorba komplexov M-prote\u00ednu s ostatn\u00fdmi bielkovinami s\u00e9ra.
      \nPr\u00ed\u010diny falo\u0161nej pozitivity:<\/em> fibrinog\u00e9n, hemopex\u00edn \u2013 hemoglob\u00ednov\u00fd komplex.<\/p>\n
      4. Imunofixa\u010dn\u00e1 elektrofor\u00e9za v s\u00e9re<\/strong> umo\u017e\u0148uje pomocou antis\u00e9r proti \u0165a\u017ek\u00fdm a \u013eahk\u00fdm re\u0165azcom ur\u010di\u0165 triedu monoklonov\u00e9ho \u00a0imu- noglobul\u00ednu (G, A, M, pr\u00edpadne D, E) a antig\u00e9nny typ \u013eahk\u00e9ho re\u0165azca (kappa a lambda). Imunofix\u00e1cia sa vykon\u00e1va v\u017edy pri n\u00edzkosekre\u010dn\u00fdch form\u00e1ch MG, napr\u00edklad AL-amyloid\u00f3zy, ako aj lie\u010den\u00fdch \u00a0pacientov, u ktor\u00fdch pomocou elektrofor\u00e9zy nie je mo\u017en\u00e9 detegova\u0165 n\u00edzku koncentr\u00e1ciu M-prote\u00ednu. Citlivos\u0165 met\u00f3dy \u00a0je okolo 0,2 g\/l.<\/p>\n
      5. Vo\u013en\u00e9 \u013eahk\u00e9 re\u0165azce kappa a lambda v s\u00e9re (V\u013dR):<\/strong> \u00a0patologick\u00fd pomer sved\u010d\u00ed o pr\u00edtomnosti klon\u00e1lnej expanzie plazmocytov alebo ich progenitorov, pr\u00edpadne o supresii nepostihnut\u00e9ho (uninvolved) \u013eahk\u00e9ho re\u0165azca v priebehu ochorenia alebo po lie\u010dbe. Koncentr\u00e1cia v s\u00e9re z\u00e1vis\u00ed od rov- nov\u00e1hy medzi ich produkciou plazmocytmi a obli\u010dkov\u00fdm kl\u00edrensom. Na posudzovanie monoklonality u pacientov so zn\u00ed\u017eenou GF sa pou\u017e\u00edvaj\u00fa modifikovan\u00e9 referen\u010dn\u00e9 intervaly pomeru kappa\/lambda (tabu\u013eka 3). Vy\u0161etrenie je indikovan\u00e9 najm\u00e4 v diagnostike MG s tvorbou preva\u017ene vo\u013en\u00fdch \u013eahk\u00fdch re\u0165azcov (AL-amyloid\u00f3za, \u013eahkore\u0165azcov\u00fd a nesekre\u010dn\u00fd myel\u00f3m), ktor\u00fdch detekcia pomocou \u00a0elektrofor\u00e9zy a imunofix\u00e1cie je problematick\u00e1. V skr\u00edningu MG je vy\u0161etrenie V\u013dR v kombin\u00e1cii s elektrofor\u00e9zou v s\u00e9re vhodnej\u0161ou a citlivej\u0161ou met\u00f3dou, ktor\u00e1 nahr\u00e1dza problematick\u00fd a nepohodln\u00fd zber mo\u010du (3).<\/p>\n
      6. Imunofixa\u010dn\u00e1 elektrofor\u00e9za v mo\u010di:<\/strong> umo\u017e\u0148uje \u00a0identifikova\u0165 pr\u00edtomnos\u0165 monoklonov\u00fdch \u00a0\u013eahk\u00fdch re\u0165azcov (Benceova-Jonesovej protein\u00faria) a intaktn\u00e9ho monoklonov\u00e9ho \u00a0Ig ako prejav neselekt\u00edvnej glomerulovej protein\u00farie pri \u0165a\u017e\u0161om po\u0161koden\u00ed obli\u010diek. Pod\u013ea s\u00fa\u010dasn\u00fdch odborn\u00fdch odpor\u00fa\u010dan\u00ed na diagnostiku a lie\u010dbu MM a pr\u00edbuzn\u00fdch MG je u v\u0161etk\u00fdch pacientov s diagnostikovan\u00fdm ochoren\u00edm po\u017eadovan\u00e9 aj imunofixa\u010dn\u00e9 vy\u0161etrenie 24-hodinov\u00e9ho mo\u010du (1, 4). D\u00f4kaz patologick\u00fdch koncentr\u00e1ci\u00ed v mo\u010di (spolu s kvantitou V\u013dR v s\u00e9re) m\u00e1 diagnostick\u00fd v\u00fdznam najm\u00e4 pri MG, pre ktor\u00e9 je charakteristick\u00e1 len tvorba V\u013dR \u2013 \u013eahkore\u0165azcov\u00fd myel\u00f3m, nesekre\u010dn\u00fd myel\u00f3m, AL-amyloid\u00f3za.<\/p>\n
      7.\u00a0 \u00a0Prietokov\u00e1 cytometria:<\/strong> stanovenie percentu\u00e1lneho zast\u00fapenia, fenotypu a klonality plazmatick\u00fdch buniek (PB) a ur\u010denie percentu\u00e1lneho podielu abnorm\u00e1lnych buniek z celkov\u00e9ho po\u010dtu PB umo\u017e\u0148uje rozl\u00ed\u0161enie najm\u00e4 medzi:<\/p>\n
        \n
      • MGUS, myel\u00f3mom a reakt\u00edvnou plazmocyt\u00f3zou<\/li>\n
      • IgM myel\u00f3mom a in\u00fdmi IgM produkuj\u00facich lymfoproliferat\u00edvnymi ochoreniami<\/li>\n<\/ul>\n
        Najvhodnej\u0161\u00edmi \u00a0identifik\u00e1tormi plazmatick\u00fdch \u00a0buniek s\u00fa antig\u00e9ny CD38 a CD138. Na pos\u00fadenie patol\u00f3gie jednotliv\u00fdch subpopul\u00e1ci\u00ed PB sa vy\u017eaduje multifarebn\u00e1 \u00a0prietokov\u00e1 cytometria \u00a0doplnen\u00e1 \u00a0aj o \u010fal\u0161ie potenci\u00e1lne \u00a0aberantn\u00e9 markery, ktor\u00e1 umo\u017e\u0148uje \u00a0odhali\u0165 aj ve\u013emi mal\u00fd patologick\u00fd klon medzi norm\u00e1lnymi PB (5).<\/p>\n
        Hodnotenie:<\/strong> N\u00e1lez \u2265 95 % patologick\u00fdch \u00a0PB s aberantn\u00fdm fenotypom sved\u010d\u00ed o MM (6).<\/p>\n
        Norm\u00e1lny fenotyp:<\/strong> CD19+CD56-.<\/p>\n
        Aberantn\u00e9 fenotypy:<\/strong> CD19-CD56+, CD19-CD56-, resp. CD19+CD56+. Medzi \u010fal\u0161ie znaky aberantn\u00e9ho fenotypu patr\u00ed:<\/p>\n
          \n
        • zn\u00ed\u017een\u00e1 expresia CD19, CD27, CD38 CD45 a CD81<\/li>\n
        • zv\u00fd\u0161en\u00e1 expresia CD28, CD33, CD56, CD200<\/li>\n
        • asynchr\u00f3nna expresia CD20 a CD117<\/li>\n<\/ul>\n
          Na ur\u010denie klonality sa stanovuje pomer cytoplazmatick\u00fdch \u013eahk\u00fdch re\u0165azcov kappa\/lambda, ktor\u00fd je v polyklonov\u00fdch PB v rozmedz\u00ed \u00a00,3 \u2013 3,0. Stanovenie \u00a0cytoplazmatickej \u00a0expresie re\u0165azcov kappa a lambda je nevyhnutn\u00e9 v nejasn\u00fdch pr\u00edpadoch, na vyl\u00fa\u010denie pacientov bez MG, pri MGUS a asymptomatickom MM, ako aj pri anal\u00fdze minim\u00e1lnej \u00a0rezidu\u00e1lnej choroby.<\/p>\n
          Limit\u00e1cia: <\/em>V porovnan\u00ed s konven\u010dnou \u00a0mikroskopiou je percento \u00a0PB detegovan\u00e9 prietokovou cytometriou podhodnoten\u00e9 v d\u00f4sledku hemodil\u00facie vzorky kostnej drene a depl\u00e9cie lipidoadhez\u00edvnych plazmocytov.<\/p>\n
           <\/p>\n
          D<\/strong>\u00f4ka<\/strong>z org\u00e1nov\u00e9ho postihnutia<\/strong><\/p>\n
          Na odhalenie org\u00e1nov\u00fdch komplik\u00e1ci\u00ed (tabu\u013eka 4) sl\u00fa\u017eia laborat\u00f3rne vy\u0161etrenia: kompletn\u00fd KO, urea, kreatin\u00edn, GF, Ca, album\u00edn, LD, CRP, Ig GAM kvantitat\u00edvne, V\u013dR. Nov\u00e9 revidovan\u00e9 \u00a0krit\u00e9ri\u00e1 IMGW (international Myeloma \u00a0Working Group, 2014) pre diagnostiku mnohopo\u010detn\u00e9ho myel\u00f3mu zah\u0155\u0148aj\u00fa 3 nov\u00e9 valido- van\u00e9 biomarkery, ktor\u00e9 sa prid\u00e1vaj\u00fa k tradi\u010dn\u00fdm markerom org\u00e1nov\u00e9ho postihnutia \u00a0a umo\u017enia skupine r\u00fdchlo progreduj\u00facich pacientov s asymptomatick\u00fdm (smoldering) myel\u00f3mom profitova\u0165 z v\u010dasnej\u0161ej lie\u010dby (8).<\/p>\n
          Pr\u00edtomnos\u0165 aspo\u0148 jedn\u00e9ho z nasleduj\u00facich troch krit\u00e9ri\u00ed posta\u010duje \u00a0pre diagn\u00f3zu MM bez oh\u013eadu na pr\u00edtomnos\u0165 markerov CRAB:<\/p>\n
            \n
          1. zast\u00fapenie \u00a0klon\u00e1lnych \u00a0buniek v kostnej dreni \u2265 60 %<\/li>\n
          2. pomer \u00a0postihnut\u00fd\/nepostihnut\u00fd \u00a0V\u013dR \u2265 100<\/li>\n
          3. viac ako jedna l\u00e9zia nad 5 mm zisten\u00e1 pomocou\u00a0 MRI<\/li>\n<\/ol>\n
            IMWG upozornila aj na \u010fal\u0161ie s\u013eubn\u00e9 biomarkery, ktor\u00e9 by v bud\u00facnosti mohli by\u0165 s\u00fa\u010das\u0165ou diagnostick\u00fdch krit\u00e9ri\u00ed pre mnohopo\u010detn\u00fd \u00a0myel\u00f3m:<\/p>\n
              \n
            • v\u00fdskyt abnorm\u00e1lneho imunofenotyp plazmatick\u00fdch buniek \u2265 95%;<\/li>\n
            • imunosupresia norm\u00e1lnych imunoglobul\u00ednov;<\/li>\n
            • progresia asymptomatick\u00e9ho myel\u00f3mu v podobe n\u00e1rastu M-prote\u00ednu o \u226510 % v dvoch po sebe id\u00facich vy\u0161etreniach v priebehu 6 mesiacov;<\/li>\n
            • cytogenick\u00e9 subtypy t(4;14), 1q amp alebo del 17p;<\/li>\n
            • nevysvetlen\u00fd pokles GF o \u00a0\u226525 % plus n\u00e1rast protein\u00farie alebo koncentr\u00e1cie V\u013dR v s\u00e9re.<\/li>\n<\/ul>\n
               <\/p>\n
              V<\/strong>y<\/strong>\u0161e<\/strong>t<\/strong>r<\/strong>e<\/strong>ni<\/strong>e prognostick\u00fdch markerov<\/strong><\/p>\n
                \n
              1. Medzin\u00e1rodn\u00fd\u00a0 st\u00e1\u017eovac\u00ed syst\u00e9m na ur\u010dovanie klinick\u00fdch \u0161t\u00e1di\u00ed myel\u00f3mu \u2013 International Staging System for Multiple Myeloma \u00a0(8), je zalo\u017een\u00fd na jednoduch\u00fdch a \u0161iroko dostupn\u00fdch laborat\u00f3rnych vy\u0161e- treniach \u2013 s\u00e9rov\u00fdch koncentr\u00e1ci\u00e1ch \u03b22-mikroglobul\u00ednu \u00a0a album\u00ednu (tabu\u013eka 5).<\/li>\n
              2. Vo\u013en\u00e9 \u013eahk\u00e9 re\u0165azce kappa a lambda v s\u00e9re:<\/strong> patologick\u00e1 koncentr\u00e1cia V\u013dR je nepriazniv\u00fdm prognostick\u00fdm \u00a0faktorom pri v\u00e4\u010d\u0161ine \u00a0MG, nevyn\u00edmaj\u00fac MGUS (tabu\u013eka \u00a06). Koncentr\u00e1cia monoklonov\u00fdch V\u013dR koreluje nielen s ve\u013ekos\u0165ou n\u00e1dorovej hmoty, ale aj s rizikom obli\u010dkov\u00e9ho po\u0161kodenia. V monitorovan\u00ed priebehu ochorenia alebo efektu lie\u010dby sa odpor\u00fa\u010da okrem pomeru \u00a0V\u013dR sledova\u0165 aj absol\u00fatnu koncentr\u00e1ciu postihnut\u00e9ho typu re\u0165azca alebo diferenciu medzi postihnut\u00fdm a ne- postihnut\u00fdm re\u0165azcom, ktor\u00e1 lep\u0161ie odr\u00e1\u017ea ve\u013ekos\u0165 n\u00e1dorovej masy (4).<\/li>\n
              3. Prietokov\u00e1 cytometria:<\/strong> participuje pri ur\u010den\u00ed rizika progresie u pacientov s MGUS a asymptomatick\u00fdm mnohopo\u010detn\u00fdm \u00a0myel\u00f3mom detekciou percentu\u00e1lneho podielu abnorm\u00e1lnych PB z celkov\u00e9ho po\u010dtu plazmatick\u00fdch buniek. N\u00e1lez \u2265 95 % patologick\u00fdch PB s abnorm\u00e1lnym fenotypom sved\u010d\u00ed o transform\u00e1cii MGUS do MM.<\/li>\n
              4. Prognostick\u00e9 cytogenetick\u00e9 markery: MM sa vyzna\u010duje \u0161pecifick\u00fdmi abnormalitami chromoz\u00f3mov, ktor\u00e9 umo\u017e\u0148uj\u00fa rizikov\u00fa stratifik\u00e1ciu, najm\u00e4 pacientov lie\u010den\u00fdch vysokod\u00e1vkovanou chemoterapiou s podporou autol\u00f3gnej transplant\u00e1cie kme\u0148ov\u00fdch buniek a biologickej lie\u010dby (tabu\u013eka 7). Minim\u00e1lny panel odpor\u00fa\u010dan\u00fdch FISH vy\u0161etren\u00ed u pacientov s myel\u00f3mom (tzv. \u201ehigh-risk panel\u201c) zah\u0155\u0148a:
                \n\u2013 translok\u00e1cie t(4;14)(p16;q32), t(14;16)(q32;q23)
                \n\u2013 del\u00e9cia TP53 [del(17)(p13)]
                \n\u2013 zisk\/amplifik\u00e1cia v oblasti 1q21 (CKS1B)
                \nS\u00fa\u010dasn\u00e1 pozitivita translok\u00e1cie a najmenej jednej \u010fal\u0161ej chromoz\u00f3movej abnormality definuje vysokorizikov\u00fdch pacientov s nepriaznivou progn\u00f3zou. Roz\u0161\u00edren\u00fd panel cytogenick\u00fdch prognostick\u00fdch markerov sa pou\u017e\u00edva u pacientov lie\u010den\u00fdch imunomodula\u010dn\u00fdmi liekmi a inhib\u00edtormi proteaz\u00f3mu (1).<\/li>\n<\/ol>\n
                 <\/p>\n
                M<\/strong>on<\/strong>i<\/strong>to<\/strong>r<\/strong>ovanie lie\u010dby<\/strong><\/p>\n
                Medzin\u00e1rodn\u00e9 krit\u00e9ri\u00e1 IMWG (International Myeloma Working Group, 2006) na hodnotenie lie\u010debnej odpovede zah\u0155\u0148aj\u00fa aj nasledovn\u00e9 laborat\u00f3rne parametre (9):<\/p>\n
                  \n
                1. M-gradient \u00a0v elektrofor\u00e9ze: \u00a0<\/strong>Pou\u017e\u00edva sa pr\u00edpade tzv. merate\u013enej choroby, ktor\u00e1 je definovan\u00e1 \u00a0ako M-gradient nad 10 g\/l v s\u00e9re a\/alebo \u00a0nad 0,2 g\/24 \u00a0hod. v mo\u010di. Idiotyp M-prote\u00ednu sa v priebehu v\u00fdvoja myel\u00f3mu nemen\u00ed, hoci ojedinele, najm\u00e4 pri relapse ochorenia m\u00f4\u017eu myel\u00f3mov\u00e9 \u00a0bunky strati\u0165 schopnos\u0165 \u00a0tvorby \u0165a\u017ek\u00fdch re\u0165azcov a ochorenie pokra\u010duje ako \u013eahkore\u0165azcov\u00fd myel\u00f3m. Ve\u013emi zriedkavo je pozorovan\u00e1 prechodn\u00e1 zmena izotypu Ig a pr\u00edtomnos\u0165 abnorm\u00e1lnych oligoklonov\u00fdch \u00a0pr\u00fa\u017ekov, ktor\u00e9 s\u00fa pova\u017eovan\u00e9 \u00a0za prejav obnovy norm\u00e1lnej tvorby imunoglobul\u00ednov a s\u00fa spojen\u00e9 s lep\u0161\u00edm pre\u017e\u00edvan\u00edm.<\/li>\n
                2. Vo\u013en\u00e9 \u013eahk\u00e9 re\u0165azce v s\u00e9re:<\/strong> Krit\u00e9ri\u00e1 lie\u010debnej odpovede \u00a0IMWG odpor\u00fa\u010daj\u00fa kvantitat\u00edvne stanovenie V\u013dR pri hodnoten\u00ed lie\u010dby v pr\u00edpadoch tzv. nemerate\u013enej choroby, t. j. oligo- \u00a0a neskeretorick\u00fdch foriem ochorenia, pri ktor\u00fdch M-prote\u00edn \u00a0nie je merate\u013en\u00fd in\u00fdmi met\u00f3dami. Podmienkou \u00a0pou\u017eitia V\u013dR v hodnoten\u00ed lie\u010debnej odpovede \u00a0je ich minim\u00e1lna \u00a0baz\u00e1lna koncentr\u00e1cia \u2265 100 mg\/l a patologick\u00fd pomer. V kateg\u00f3rii \u00faplnej remisie, tzv. stringent complete response <\/em>sa okrem ch\u00fdbania imunohistochemick\u00fdch \u00a0a imunofluorescen\u010dn\u00fdch zn\u00e1mok monoklonality vy\u017eaduje aj norm\u00e1lny pomer V\u013dR v s\u00e9re (tabu\u013eka 8). Pomocou \u00a0stanovenia V\u013dR v s\u00e9re je mo\u017en\u00e9 diagnostikova\u0165 tzv. \u201elight chain escape\u201c fenom\u00e9n, j. objavenie \u00a0sa dediferencovan\u00e9ho \u00a0klonu buniek produkuj\u00facich len monoklonov\u00e9 V\u013dR, ktor\u00e9 nereaguj\u00fa \u00a0na lie\u010dbu.<\/li>\n
                3. Prietokov\u00e1 cytometria:<\/strong> Pri detekcii minim\u00e1lnej rezidu\u00e1lnej choroby u lie\u010den\u00fdch pacientov s mnohopo\u010detn\u00fdm myel\u00f3mom stanoven\u00edm pr\u00edtomnosti abnorm\u00e1lnych plazmatick\u00fdch buniek.<\/li>\n
                4. Monitorovanie obli\u010dkovej choroby:<\/strong> Po\u0161kodenie obli\u010diek je pr\u00edtomn\u00e9 u 20 \u2013 50 % pacientov s myel\u00f3mom. V jeho patogen\u00e9ze sa uplat\u0148uje najm\u00e4 \u00a0nefrotoxicita V\u013dR, ktor\u00fa potenciuj\u00fa \u00a0\u010fal\u0161ie faktory ako dehydrat\u00e1cia, hyperkalci\u00e9mia \u00a0a nefrotoxick\u00e9 \u00a0lie\u010div\u00e1. Denn\u00e1 produkcia \u00a0V\u013dR okolo 5 g je u v\u00e4\u010d\u0161iny pacientov spojen\u00e1 s nefrotoxick\u00fdmi \u00fa\u010dinkami. Ve\u013ek\u00e9 mno\u017estv\u00e1 prefiltrovan\u00fdch V\u013dR prekra\u010duj\u00fa reabsorp\u010dn\u00fa \u00a0kapacitu proxim\u00e1lnych tubulov, \u010do vedie k vzniku preren\u00e1lnej (Benceovej-Jonesovej) protein\u00farie a n\u00e1sledn\u00e9mu po\u0161kodeniu t<\/em>ub<\/em>u<\/em>l<\/em>o<\/em>i<\/em>n<\/em>t<\/em>ers<\/em>t<\/em>\u00ed<\/em>c<\/em>i<\/em>a<\/em>. Klinick\u00e9 prejavy var\u00edruj\u00fa od Fanconiho syndr\u00f3mu cez tzv. myel\u00f3mov\u00fa \u00a0obli\u010dku (cast nephropathy) a\u017e po ak\u00fatne oligurick\u00e9 zlyhanie obli\u010diek v d\u00f4sledku mas\u00edvnej ob\u0161trukcie dist\u00e1lnych aj proxim\u00e1lnych tubulov (10). In\u00e9 typy \u013eahk\u00fdch re\u0165azcov p\u00f4sobia nefrotoxicky na \u00farovni gl<\/em>o<\/em>m<\/em>e<\/em>r<\/em>ul<\/em>o<\/em>v<\/em>, pri\u010dom vyvol\u00e1vaj\u00fa dve rozdielne formy po\u0161kodenia \u2013 AL-amyloid\u00f3zu a chorobu z ukladania \u013eahk\u00fdch re\u0165azcov (LCDD), ktor\u00fdch hlavn\u00fdm klinick\u00fdm prejavom je neselekt\u00edvna glomerulov\u00e1 protein\u00faria nefrotick\u00e9ho typu. Stanovenie V\u013dR je pr\u00ednosom v diferenci\u00e1lnej diagnostike vymenovan\u00fdch\u00a0 ochoren\u00ed obli\u010diek a pri hodnoten\u00ed \u00a0\u00fa\u010dinnosti elimina\u010dnej lie\u010dby pomocou nov\u00fdch hemodialyz\u00e1torov s ve\u013ekos\u0165ou p\u00f3rov, ktor\u00e9 dovo\u013euj\u00fa prechod molek\u00fal V\u013dR \u2013 tzv. \u201ehigh cut-off dialyzer\u201c.<\/li>\n<\/ol>\n
                   <\/p>\n
                  Predanalytick\u00e9 inform\u00e1cie<\/strong>
                  \nOdber<\/strong>
                  \nParametre v s\u00e9re:<\/strong> \u0161tandardn\u00e1 g\u00e9lov\u00e1 sk\u00famavka, nie s\u00fa potrebn\u00e9 \u0161peci\u00e1lne podmienky pri odbere a transporte.
                  \nImunofix\u00e1cia v mo\u010di:<\/strong> jednorazov\u00fd alebo zbieran\u00fd mo\u010d (24-hodinov\u00fd zber, ak je potrebn\u00e1 kvantifik\u00e1cia M-gradientu v mo\u010di).
                  \nPrietokov\u00e1 cytometria:<\/strong> odber perif\u00e9rnej krvi ako na krvn\u00fd obraz.<\/p>\n
                  Interferencie<\/strong>
                  \nPri stanoven\u00ed CB, Ig a V\u013dR interferuje siln\u00e1 hemol\u00fdza a lip\u00e9mia.
                  \nElektrofor\u00e9za: vy\u0161etrenie v plazme imituje pr\u00edtomnos\u0165 M-gradientu v beta2globul\u00ednoch
                  \n(fibrinog\u00e9n), hemol\u00fdza imituje M-gradient v alfa2globul\u00ednoch.<\/p>\n
                   <\/p>\n
                  Literat\u00fara<\/strong>
                  \n1. Doporu\u010den\u00ed \u010cesk\u00e9 myelomov\u00e9 skupiny, Myelomov\u00e9 sekce \u010cesk\u00e9 hematologick\u00e9 spole\u010dnosti a Slovenskej myel\u00f3movej spolo\u010dnosti. Diagnostika a l\u00e9\u010dba mnoho\u010detn\u00e9ho myelomu. Transfuze a hematologie dnes. 2012;18(suppl1 2):1\u201389.
                  \n2. Bradwell AR. Serum free light chain analysis (plus Hevylite). 7th ed. Birmingham: The Binding Site Ltd.; 2014: 312.
                  \n3. Katzmann JA, Dispenzieri A, Kyle RA, et al. Elimination of need for urine studies in the screening algorithm for monoclonal gammopathies by using serum immunofixation and free light chain assay. Mayo Clinic Proceedings. 2006;81(12):1575\u20131578.
                  \n4. Dispenzieri A, Kyle RA, Merlini G, et al. International myeloma working group guidelines for serum free light chain analysis in multiple myeloma and related disorders. Leukemia. 2009;23:215\u2013224.
                  \n5. Rawstron A, Orfao A Beksac M, et al. Report of the European Myeloma Network on multiparametric flow cytometry in multiple myeloma and related disorders. Haematologica. 2008;93(3):431\u2013438.
                  \n6. Paiva B, Almeida J, P\u00e9rez-Andr\u00e9s M, et al. Utility of flow cytometry immunophenotyping in multiple myeloma and other clonal plasma cellrelated disorders. Cytometry B Clin Cytom. 2010;78(4):239\u201352.
                  \n7. Rajkumar SV, Dimopoulos MA, Palumbo A, et al. International Myeloma Working Group updated criteria for diagnosis of multiple myeloma. Lancet Oncol. 2014;15:E538
                  \n8. Greipp PR. International staging system for multiple myeloma. J Clin Oncol. 2005;23(15):3412\u22123420.
                  \n9. Durie BG, et al. International uniform response criteria for multiple myeloma. Leukemia 2006; 20(10):1\u22127.
                  \n10. Hutchinson CA, et al. Efficient removal of immunoglobulin free light chains by hemodialysis for multiple myeloma: in vitro and in vivo studies. J Am Soc Nephrol. 2007;17:886\u221289.
                  \n11. Luka\u010dkov\u00e1 R, Mladosievi\u010dov\u00e1 B. Rizikov\u00e1 stratifik\u00e1cia pacientov s mnohopo\u010detn\u00fdm myel\u00f3mom pod\u013ea pr\u00edtomnosti genetick\u00fdch markerov. Lek\u00e1rsky obzor 2013;62(10):359\u2212362.<\/p>\n","protected":false},"excerpt":{"rendered":"
                  *All tables, charts, graphs and pictures that are featured in this article can be found in the .pdf attachment at the end of the paper.   \u00davod Klasifik\u00e1cia zalo\u017een\u00e1 na biologickom potenci\u00e1li patologick\u00e9ho bunkov\u00e9ho klonu tradi\u010dne rozli\u0161uje mal\u00edgne a ben\u00edgne MG (tabu\u013eka 1). Premal\u00edgne \u0161t\u00e1dium ochorenia, tzv. monoklonov\u00e1 gamapatia nejasn\u00e9ho v\u00fdznamu (monoclonal gammopathy of undetermined<\/p>\n","protected":false},"author":7,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_mi_skip_tracking":false,"footnotes":""},"categories":[289],"tags":[684,686,682,683,685],"class_list":["post-1086","post","type-post","status-publish","format-standard","hentry","category-biochemistry","tag-free-light-chains","tag-monitoring-of-therapeutic-response","tag-monoclonal-gammopathy","tag-monoclonal-protein","tag-prognostic-laboratory-markers","typ_clanku-review-article"],"acf":{"abstrakt":"
                  Monoclonal gammopathies (MG) represent a heterogenous group of conditions characterized by clonal proliferation of lymphoid, plasma cells or differentiated B-plasma cells with increased production of monoclonal immunoglobulin (M-protein). Multiple myeloma (MM) is the most important representative of malign MG and the second most frequent blood malignancy. Testing of serum proteins, molecular markers and genetic profiles enable diagnosing of MG, monitoring of asymptomatic phase of the disease, risk stratification of patients, assessing of prognosis, and therapeutic response in treated patients.<\/p>\n
                  Key words:\u00a0<\/strong>monoclonal gammopathy, monoclonal protein, free light chains, prognostic laboratory markers, monitoring of therapeutic response<\/p>\n","casopis":[{"ID":995,"post_author":"7","post_date":"2016-11-16 12:14:30","post_date_gmt":"2016-11-16 11:14:30","post_content":"
                  Biochemistry <\/strong><\/h4>\r\n
                    \r\n \t
                  • Biochemical inflammation markers<\/li>\r\n \t
                  • Biochemical examinations in liver diseases<\/li>\r\n \t
                  • Biochemical diagnosis in diseases of GIT<\/li>\r\n \t
                  • Hypoglycemia<\/li>\r\n \t
                  • Urolithiasis as a result of metabolic diseases<\/li>\r\n \t
                  • Indication and application of tumor markers in clinical practice<\/li>\r\n \t
                  • Monoclonal gammopathies \u2013 laboratory examinations in diagnosis and monitoring<\/li>\r\n \t
                  • Hormones in diagnosis of reproductive function disorders<\/li>\r\n \t
                  • Cerebrospinal fluid diagnosis of diseases affecting the nervous system<\/li>\r\n \t
                  • Determining trace elements in blood serum<\/li>\r\n<\/ul>\r\n
                    Genetics<\/strong><\/h4>\r\n
                      \r\n \t
                    • Assessing the therapeutic response in patients with chronic myelocyte leukemia treated with tyrosine kinase inhibitors<\/li>\r\n \t
                    • Hormones in diagnosis of reproductive functions\u2019 disorders<\/li>\r\n<\/ul>\r\n
                      Hematology <\/strong><\/h4>\r\n
                        \r\n \t
                      • Anemias \u2013 laboratory diagnosis of the most frequently prevalent types of anemia<\/li>\r\n \t
                      • Laboratory and hematological technical equipment<\/li>\r\n<\/ul>\r\n
                        Immunology <\/strong><\/h4>\r\n
                          \r\n \t
                        • Paraneoplastic neurological syndromes and in vitro diagnosis of onconeural antibodies<\/li>\r\n<\/ul>","post_title":"newslab","post_excerpt":"","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"newslab","to_ping":"","pinged":"","post_modified":"2017-08-16 21:40:20","post_modified_gmt":"2017-08-16 19:40:20","post_content_filtered":"","post_parent":0,"guid":"http:\/\/www.newslab.sk\/casopis\/newslab\/","menu_order":0,"post_type":"casopis","post_mime_type":"","comment_count":"0","filter":"raw"}],"strana":"25","upload_clanok":{"ID":1087,"id":1087,"title":"durovcova_monoklonove_gamapatie","filename":"\u010eurovcov\u00e1_Monoklonove_gamapatie.pdf","filesize":139094,"url":"https:\/\/www.newslab.sk\/wp-content\/uploads\/2016\/12\/\u010eurovcov\u00e1_Monoklonove_gamapatie.pdf","link":"https:\/\/www.newslab.sk\/en\/monoclonal-gammopathies-laboratory-tests-in-diagnosis-and-monitoring\/durovcova_monoklonove_gamapatie\/","alt":"","author":"7","description":"","caption":"","name":"durovcova_monoklonove_gamapatie","status":"inherit","uploaded_to":1086,"date":"2016-12-08 21:33:23","modified":"2016-12-08 21:33:23","menu_order":0,"mime_type":"application\/pdf","type":"application","subtype":"pdf","icon":"https:\/\/www.newslab.sk\/wp-includes\/images\/media\/document.png"}},"_links":{"self":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/posts\/1086","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/users\/7"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/comments?post=1086"}],"version-history":[{"count":0,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/posts\/1086\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/media?parent=1086"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/categories?post=1086"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/tags?post=1086"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}