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wtorek, 17 listopada 2015

interpretacja testu CD57

interpretacja testu CD57 ‏

Co bada test ?

Pacjenci z niskim mianem CD57 mają więcej koinfekcji i czują się gorzej, mają więcej objawów neurologicznych oraz więcej problemów immunologicznych; lek. med. R. Stricker rekomenduje miano CD57 jako marker postępu choroby (Ann Agric Environ Med2002, 9:111-113)

,,Test CD57  spełnia ważną rolę w diagnostyce i terapii boreliozy. Wiadome jest, ze aktywna, przewlekła choroba powoduje ubytek subpopulacji limfocytów CD57 (natural killers) stanowiących naturalną linię obrony organizmu człowieka. Badanie to jest stosunkowo niedrogie, wiarygodne i czułe, bowiem tylko zakażenie borrelia powoduje obniżenie odsetka limfocytów CD57,,.

http://emg-neurolog.pl/borelioza/

Bada ilość  limfocytów NK ( Natural Killers ) w krwi. Limfocyty te posiadają antygen powierzchniowy CD57.
Stricker i Winger zbadali, że zmniejszenie się liczby tych konkretnie limfocytów jest związane z przewlekłą choroba z Lyme. Nie jest jasne dlaczego w innych chorobach nie występuje takie zjawisko.SM, toczeń itp .

 CD57: agresywne białe ciałko krwi, jego poziom zostaje obniżony za sprawą Borrelii poprzez mechanizm który nie jest znany; pacjenci z niskim mianem CD57 mają więcej koinfekcji i czują się gorzej, mają więcej objawów neurologicznych oraz więcej problemów immunologicznych; lek. med. R. Stricker rekomenduje miano CD57 jako marker postępu choroby (Ann Agric Environ Med 2002, 9:111-113)

Spadek limfocytów CD57 może być uznany jako ważny objaw chronicznej boreliozy. Zmiany w podzbiorach CD 57 mogą być użyteczne przy monitorowaniu odpowiedzi organizmu na terapię przeciwko boreliozie".
CD57 + CD3

U mnie 47 - czyli bardzo niska ilość .
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CD57-
test, wskazywany przez Strickera, jako pomocny w monitorowaniu leczenia oraz w diagnostyce seronegatywnej boreliozy, której objawy są obecne dłużej niż 1 rok.

 Jako specyficzny dla boreliozy traktowana jest subpopulacja limfocytów CD57+ CD3-; prawidłowa wartość tego podzbioru u osób zdrowych to >200. Wartość ponad 100 świadczy o leczeniu w dobrym kierunku, a ok. 200 o tym, że można rozważać zakończenie leczenia- biorąc pod uwagę oczywiście objawy.

To badanie ma związek ...tylko z boreliozą - z koinfekcjami niestety, nie. Burrascano w swoim przewodniku leczenia z 2005 r. pisze, że raczej nie spotyka osób wyleczonych, których wartość CD57 jest poniżej 180 komórek. Innymi słowy- przy wartościach niższych nie ma co kończyć leczenia.

Wynik odzwierciedla stopień zakażenia. To nie jest test diagnostyczny, ale jest stosowany jako marker Lyme :
>200 norma
<20 ciężka choroba
0-60 chroniczna borelioza
> 60 poprawa; leczenie idzie w dobrym kierunku


Uwaga! Test nie powinien być wykonywany u dzieci ze względu na brak odniesienia do wyników obserwacji Strickera (badania robiono tylko na populacji osób dorosłych
CD 57- streszczenie artykułu Strickera

://www.ncbi.nlm.nih.gov/pubmed/11222912


Przykładowy wynik badania CD 57 (FACs na boreliozę):
Limfocytoza CD45+/SSC low 1489... norma [1000-5300]
Limfocyty T CD3+ 948 , norma [800-3500]
Limf. T supresorowe CD3+CD8+ 369 norma [200-1200]
Limf. T pomocnicze CD3+CD4+ 509 [400-2100]
Komórki NK CD16+56+CD3- 300 [70-1200]
Limfocyty B CD19+ 220 [200-600]
Stosunek Limf. T pomocn/supr 1.4 norma [1.1 - 1.4]
Subpopulacja NK:
CD 56+ CD 3- 300
CD 57+CD 8+ 129
CD 56+CD 57+ 143
CD 56+CD 3- 116
CD 57+ 192 120
CD 57 CD 3- 92
Subpopulacja T CD8+/CD57+ 49

tekst ze strony :

http://kleszcze.edu.pl/diagnostyka-laboratoryjna-w-chorobach-odkleszczowych-t121.html
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dr Burrascano:

 ,, ... U chorych na przewlekłą boreliozę z Lyme miano subpopulacji limfocytów NK CD57 jest zarówno użyteczne, jak i ważne. Możliwość oznaczenia tego miana stanowi przełom w diagnostyce i leczeniu boreliozy z Lyme. Wiadomo, że przewlekła infekcja Borrelią tłumi układ immunologiczny i obniża miano subpopulacji limfocytów NK CD57.

U chorych na boreliozę z Lyme możemy używać stopnia obniżenia miana limfocytów NK CD57, by wykazać, na ile aktywna jest borelioza i czy po zakończeniu leczenia możliwe jest wystąpienie nawrotu. To badanie może być stosowane jako prosty, niedrogi test przesiewowy, ponieważ w chwili obecnej uważa się, że tylko Borrelia obniża to miano (norma to 200). Dlatego chory z dużą liczbą limfocytów NK CD57 jest prawdopodobnie chory na coś innego niż borelioza z Lyme, lub ma koinfekcje.

 Generalnie występuje pewien stopień fluktuacji miana NK CD57 w czasie; ta liczba nie rośnie też w trakcie postępów leczenia. Zamiast tego pozostaje niska aż do czasu, gdy infekcja zostanie opanowana, wtedy liczba komórek NK CD57 skacze do góry. Jeżeli nie zawiera się w zakresie normy w czasie, gdy kończymy cykl antybiotyków, wtedy nawrót niemal z pewnością nastąpi....,,
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CONCLUSIONS:



A decrease in the CD57 lymphocyte subset may be an important marker of chronic LD. Changes in the CD57 subset may be useful to monitor the response to therapy in this disease
https://www.ncbi.nlm.nih.gov/pubmed/11222912?fbclid=IwAR0SdAXlOadmbvlwI6n8pDU2ehAhERTyIV0pKEtxEHBKusHJzKanM6Mr5ns
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,, stwierdziliśmy, że podzbiór CD3 - C57 + NK wydaje się być użytecznym markerem immunologicznym u pacjentów z uporczywymi objawami boreliozy z Lyme ,,

https://cvi.asm.org/content/16/11/1704?fbclid=IwAR3auTrGo1nbvyNgpe_2NB9ezYoIEjrsCm-522HSWs6xtDEZyadihFHeGDA
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Linki do opisow testu CD57

2014
http://www.publichealthalert.org/role-of-c3a-and-c4a-complement-proteins-in-chronic-lyme-disease.html
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http://www.publichealthalert.org/everything-you-always-wanted-to-know-about-the-cd-57-test-but-were-too-sick-to-ask.html
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2010
http://www.publichealthalert.org/stephen-buhner-lyme-treatment-update.html

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2009
http://www.publichealthalert.org/partnering-with-patients-a-team-approach-murray-r-susser-md-part-ii.html
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Inne zastosowanie testu CD 57  :

Współczesne możliwości w diagnozowaniu aft nawracających (RAS)

Diagnostyka chorób błony śluzowej jamy ustnej napotyka na największe problemy w przypadku tych chorych, u których stwierdza się występowanie wykwitów o charakterze pęcherzy, nadżerek lub owrzodzeń. Postawienie właściwego rozpoznania, a co za tym idzie wybór postępowania terapeutycznego, wymaga od lekarza praktyka aktualnej wiedzy z zakresu etiopatogenezy chorób, które najczęściej nie są do końca wyjaśnione. Wydaje się, że mechanizmy immunologiczne odgrywają zasadniczą rolę i odpowiadają za występowanie wielu zmian patologicznych błony śluzowej
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Badania komórek krążących prawdopodobnie niedokładnie odzwierciedlają zjawiska zachodzące miejscowo. Savage i wsp. (15) potwierdzają dane Pedersena (10) o obecności komórek CD 57 + w owrzodzeniach aftowych podczas trwania fazy wczesnej, bezpośrednio poprzedzającej pojawienie się wykwitów. Nie udało się jednak wykazać obecności tych komórek w fazie późnej. Pomimo że przeciwciało przeciw CD 57 nie wykrywa specyficznie obecności komórek NK można przypuszczać, że komórki te odgrywają pewną rolę we wczesnych etapach choroby.,,
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Natural Killer Cell Counts Are Not Different between Patients with Post-Lyme Disease Syndrom and Controls

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2725528/

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What is needed is a better Lyme test or some other objective measure to persuade the practitioner to consider the diagnosis of chronic Lyme disease. Enter the CD57 test!

You may have heard the term “CD57? tossed around on chat groups, or your Lyme-literate health care provider may have even explained the test to you in one of your moments of brain-fogged stupor.

What is this number that sounds more like a type of Heinz steak sauce than a lab test, and what in the world does it have to do with Lyme disease?   
 Let’s start by going back to basic high school biology. You may remember that white blood cells (a.k.a. leukocytes) are the components of blood that help the body fight infections and other diseases. White blood cells can be categorized as either granulocytes or mononuclear leukocytes. Mononuclear leukocytes are further sub-grouped into monocytes and lymphocytes. Lymphocytes, found in the blood, tissues and lymphoid organs, attack antigens (foreign proteins) in different ways. The main lymphocyte sub-types are B-cells, T-cells and natural killer (NK) cells. B-cells make antibodies that are stimulated by infection or vaccination. T-cells and NK cells, on the other hand, are the cellular aggressors in the immune system and are our main focus in the discussion that follows.  Let’s pause a moment and introduce something you probably never learned about in high school biology class: CD markers. CD, which stands for “cluster designation”, is a glycoprotein molecule on the cell surface that acts as an identifying marker. Think of comparing cells as comparing people. Humans are made up of innumerable superficial identifying characteristics (such as hair color, eye color, etc.) and so are cells. Cells probably have thousands of different identifying markers, or CDs, expressed on their surfaces, but 200 or so have been recognized and named so far. Each different marker (or CD) on a cell is named with a number, which signifies nothing more than the order in which the CD was discovered. On any given cell there are many different cluster designation markers (CDs), giving each cell its unique appearance and function but also linking certain cells by their similarities (like grouping all people with brown hair or all people with blue eyes). Cells that have a certain kind of CD present on their surface are denoted as + for that CD type (e.g., a cell with CD57 markers on its surface is CD57+).  NK cells have their own specific surface markers. The predominant marker is CD56. The percentage of CD56+ NK cells is often measured in patients with chronic diseases as a marker of immune status: the lower the CD56 level, the weaker the immune system. You may have heard Chronic Fatigue Syndrome patients talk about their CD56 counts. A smaller population of NK cells are CD57+. A below-normal count has been associated with chronic Lyme disease by the work of Drs. Raphael Stricker and Edward Winger. No one knows for sure why CD57+ NK cells are low in Lyme disease patients, but it is important to note that many disease states that are often confused with chronic Lyme (MS, systemic lupus, rheumatoid arthritis) are not associated with low CD57+ NK counts. The good news is that for most Lyme patients the CD57+ NK level increases as treatment progresses and health is regained.  CD57 markers can also be expressed on other kinds of cells, including T-cells, so it is important to distinguish between CD57+ T-cells and CD57+ NK cells. Clinicians need to be aware that many testing laboratories claiming to perform the CD57 test are actually looking at CD57+ T-cells rather than CD57+ NK cells, which are the cells of interest in chronic Lyme disease. In order for a testing laboratory to measure the CD57+ NK level, it first measures the percentage of lymphocytes that are CD57+ NK cells. Then an absolute count is calculated by multiplying that percentage by the patient’s total lymphocyte count. The standard normal range for the absolute CD57 NK count is 60 to 360 cells per microliter of blood. This wide range was established based upon test results of hundreds of healthy patients.  By these laboratory standards, a test result below 60 cells per microliter would be considered below normal and therefore associated with chronic Lyme disease. However, a recent study of my Austin patients has led me to believe that 100 cells per microliter is a more reliable threshold separating Lyme patients and healthy controls.  When Drs Stricker and Winger discovered that CD57+ NK cells are low in chronic Lyme patients and tend to increase with patients’ clinical improvement, an opportunity arose for Lyme-literate practitioners to utilize a handy tool to aid in the diagnosis of chronic Lyme disease, to follow treatment progress, and to determine treatment endpoint. Just as AIDS patients have always held great store in their CD4 T-cell count, Lyme patients now have a fairly reliable marker of the status of their illness.
It is important to remember that the CD57 result is just a number; far more important is the patient’s clinical status. An old professor of mine used to say, “treat the patient, not the lab test!” There is still much we do not know about the CD57 marker and what other factors may lower or raise it. However, overall, the CD57+ NK count is a useful tool in diagnosing and treating chronic Lyme disease in most patients. As a measure of immune status, it provides an indirect measure of bacterial load and severity of illness. Furthermore, in a patient who has a negative or indeterminate Lyme test but is highly suspect for the disease, the clinician may utilize the CD57+ NK count as one more piece in the complex puzzle of a Lyme disease diagnosis.

http://www.researchednutritionals.com/information.cfm?ID=200
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Abstract

In the present study we have identified and characterized three subpopulations of peripheral blood NK cells based on the surface expression of CD56 and CD16. We have designated these subsets CD16neg, CD16dim, and CD16bright according to the relative surface density of CD16. The CD16bright subset comprised about 10% to 15% of PBL, whereas the CD16dim and CD16neg subsets comprise less than 1% of the total lymphocytes. A detailed characterization of these subsets revealed both similarities and differences. The three subsets shared a great deal of phenotypic similarity, expressing CD2, CD7, CD11b, CD38, CD45R, CD18, and the p75 IL-2R on the majority of the cells in each subset. There were, however, several prominent phenotypic differences, particularly in the expression of CD57, CD11c, CD44, CD25, Leu-8, L263, and L265. The CD16neg cells were morphologically large agranular lymphocytes and demonstrated low levels of non-MHC restricted cytolysis of NK-sensitive tumor lines. The CD16dim and CD16bright subsets were large granular lymphocytes and revealed potent cytotoxicity against NK-sensitive targets. All subsets demonstrated IL-2-dependent activation and proliferation; however, the CD16dim and CD16neg subsets were preferentially responsive to very low concentrations of rIL-2. Although rIL-4 effectively inhibited the IL-2-induced cytolytic activation of all three NK cell subsets, only the CD16bright cells showed rIL-4 inhibition of IL-2 dependent proliferation. Cytokine transcription was also differentially regulated in the NK cell subsets after rIL-2 activation. Although TNF-alpha was equally transcribed in each subsets, IFN-gamma and serine protease-HF were preferentially transcribed in the CD16bright NK cells. Based on these results, we propose that these NK cell subsets represent portions of the NK cell differentiation pathway present in the peripheral blood.

 https://www.ncbi.nlm.nih.gov/pubmed/2530273
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Natural killer (NK) cells are a subset of lymphocytes composing 5% to 20% of peripheral blood mononuclear cells (PBMCs) in humans. NK cells participate in the innate immune response and play an important role in the defense against viral infections as well as in tumor surveillance and are also involved in shaping adaptive immune responses through their production of cytokines. Recently, studies have shown that NK cells share features with B and T cells of the adaptive immune system, as mouse NK cells demonstrate immune memory after viral infection.
In humans, 2 NK-cell subsets have been characterized according to the cell-surface density of CD56 and expression of CD16 (FcγRIIIa). CD56dimCD16bright NK cells compose approximately 90% of circulating NK cells; CD56brightCD16−/dim NK cells constitute approximately 10%. CD56bright NK cells proliferate and produce interferon-γ (IFN-γ) in response to stimulation with interleukin-12 (IL-12), whereas CD56dim NK cells are more cytolytic and produce significant amounts of cytokine when their activating receptors are engaged. The CD56dim NK cells differentiate from the CD56bright NK cells., NK cells are a heterogeneous population with respect to the expression of killer cell immunoglobulin-like receptors (KIR), NKG2A, and natural cytotoxic receptors.
Similar to NK cells, CD8+ T cells are crucial to the recognition and clearance of virus-infected cells. Chronic stimulation of T cells, which occurs during rheumatoid arthritis, multiple myeloma, and cytomegalovirus and HIV infections, and after bone marrow transplantation, can result in the development of CD8+ T cells that are capable of cytokine secretion yet are incapable of cell division., Such failure to proliferate is generally attributed to replicative senescence or “clonal exhaustion” resulting from continual stimulation by antigens and/or cytokines. The expression of CD57 correlates with senescence in human CD8+ T cells. CD57 is a terminally sulfated glycan carbohydrate, which is commonly expressed on T cells in persons with chronic immune activation. CD57+ T cells increase in frequency with age. CD57+CD8+ and CD57+CD4+ T cells produce IFN-γ but are unable to proliferate in response to cognate peptide. Furthermore, CD57+ lymphocytes have undergone more rounds of cell division compared with CD57 memory T cells, and expression of CD57 correlates with T cells susceptible to activation-induced cell death (AICD). Although CD57 is generally regarded as a marker of senescence in CD8+ T cells,,, a recent study showed that CD57+CD8hi T cells are capable of proliferation in response to other stimuli. Thus, CD57+ T cells may not be “end-stage” effector T cells incapable of proliferation but may represent a highly differentiated subset of T cells capable of rapid cell division, cytotoxicity, and IFN-γ production, as well as secretion of IL-5.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2981540/

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CD57 CELLS COUNT
In chronic Lyme Borreliosis, the CD57 count is both useful and important. CD57+/CD3- cells are a subset of natural killer (NK) cells. NK cells play a crucial function in innate immunity, recognizing and killing virus-infected cells and tumor cells. Dr. Stricker and collaborators (Stricker & Winger 2001; Stricker et al. 2002) reported that the number of CD57+/CD3- cells was decreased in chronic (not acute) Lyme disease. Although acute infections can be treated with antibiotics, failure to treat may result in a chronic, debilitating illness characterized by musculoskeletal and neurologic symptoms. Chronic Lyme disease may be difficult to treat, but also to diagnose (Aguero-Rosenfeld et al. 2005).
The number of CD57+/CD3- cells is decreased in chronic Lyme disease patients, particularly those with pronounced neurologic symptoms. Patients with low CD57 have significantly more co-infections and persistent immunologic defects than patients with higher counts. In patients that respond to antibiotic therapy, the number will come back to normal following treatment, but in patients with persistent Lyme disease, CD57 levels remain low. The assay is a three-color flow-cytometry-based assay. Whole blood is stained with antibodies directed against the CD3 and the CD57 antigens; the absolute number of CD57-positive/ CD3-negative lymphocytes (cells per μl of whole blood) is determined by flow-cytometry. Result indicates the absolute number of CD57+/CD3- cells (cells/μl). The normal range is 60-360 cells/μl. Untreated, chronic Lyme disease patients have values below 60.
Of note, low CD57 count was also evidenced in autistic children (Siniscalco et al. 2016). This might also point to the importance of multiple infections in autism-spectrum disorders.
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Zdiecie - mój test 09-2015 wynik 47 a powinno być 300

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