Mishkova, R.

Radkov, M.

Yordanova, E.

English

Varna Medical University Press: Journals

STUDY ON T H E S E R U M L E V E L S OF IMMUNOGLOBULINS lgG, igM, IgA IN MALIGNANT HEMOPATH1ES E . Yordanova, M. Radkov, R. Mishkova The immune response of the organism is associated wi th definite immuno-globulin types' formation (8, 9) . The antibodies, resp. immunoglobulins turn to be factors of the natural and acquired protection of the organism. In the past few years, the surge of interest in their serum level changes in various affections has led to the more extensive application of immunologic methods for their determination and follow up (4, 5) . Researches by many-authors, and personal observations as wel l , show that quantitative changes in the serum levels of immunoglobulins occur in blood diseases too ( 1 , 2, 3, 6, 7, 11, 12). I n this reports the results of purposeful studies on 122 patients wi th ma-lignant hemopathies, undergoing treatment at the hematological c l in ic of the Medical Facul ty — Varna , over the period 1971 — 1973, are described. Our aim has been to establish to wrhat degree do quantitative changes in the serum level of immunoglobulins reflect the modifications in humoral immunity oi the organism in various blood affections. Material and Methods The changes in serum level of the immunoglobulins l gG , IgM and IgA were traced out in the listed below systemic blcod diseases: leukosis - - total 55 patients (45.08 per cent), of them with acute leukosis— 22,chronic lympha-t ic leukosis — 2 1 , chronic myelogenic leukosis — 12; in patients wi th malignant lymphoblastoma — totall ing 31 (25.42 per cent), of them wi th lymphogranulomatosis — 2 1 , lymphosarcoma — 4, retotheliosarcoma — 6; in patients with reticulosis — totall ing 22 (18.03 per cent), of them wi th myeloma — 9', benign reticulosis (infectious mononucleosis) — 3, idiopath-ic reticulosis — 10; in patients wi'th hemorrhagic diathesis — total l ing 8 (6.55 per cent), of them wi th hemophilia — 4, thrombocytopenia — 4; and in 6 patients (4.92 per cent) w i th polycythemia vera (erythremia). According to sex the patients are distributed as follows: men — 84 (68.85 per cent), women — 38 (31.15 per cent), a l l w i th ages ranging from 16 to 88 years. Quantitative determination of the serum immunoglobulins was made after the method of Mancini and co-authors (10). Monospecific sera, obtained from the Center of Infectious and Paras i t ic Diseases in Sofia, Beh-ringwerke ( F . R . Germany) and Hyland ( U S A ) were used. The mean values of serum immunoglobulins in 300 healthy subjects — blood donors from the district blood-transfusion s t a t i o n — V a r n a , served as controls. The 11 Scripta scientifica medica 1 162 Е. Yordanova, М. Radkov, R. Mishkova changes in the serum levels of immunoglobulins were checked in the early stage of the disease (onset), in the course of treatment, after treatment was completed, and during the recurrence period. In addition, the patients were subjected to the following paraclinical examinations: peripheral blood pic­ture (hemoglobin, erythrocytes, leukocytes and differential count), erythro­cyte sedimentation rate, hepatic flocculation tests (Weltmann and thymol turbidity test), total proteins and proteinogram, transaminases, a lkal ine phosphatase and fibrinogen. Results and Discussion The changes found in the serum levels of immunoglobulins in the various^ types of systemic blood diseases are summed up and presented in Figure 1. Fig . 1. serum immunoglobulin changes in blood diseases. / — controls, 2 — leukosis, 3 — malignant lymphoblastomatosis, 4 — reticulosis, 5 — hemorrhagic diathesis. I n the leukosis group, the serum immunoglobulins show an overall in­crease in levels, better pronounced in class I g G and IgM (p<0 .01) . I n class IgA the rise is less pronounced as compared to IgA values in the controls ( p > 0 . 3 ) . B y type of leukosis affection, the changes in immunoglobulins display the following peculiarities: in the acute leukosis group the mean Study on the Serum Leveis of Immunoglobulins. 163 values of the three immunoglobulin classes are significantly increased (p <0.01) . I n chronic lymphatic leukosis the mean values of I gG are moderate­ly increased (p<0 .05 ) , while the other two immunoglobulin classes — IgM and IgA — exhibi t a fal l of the serum level . The lowering is mostly marked in IgM (95 ± 1 0 mg, p<0 .01 ) , while in IgA it is but sl ightly pro-2000 1800 1600 1400 1200 200 100 Fig . 2. Changes in the serum levels of immunoglobulins in leukosis. nounced ( 1 7 6 ± 1 2 5 mg, p > 0 . 3 ) . The data referred to are i l lustrated in F i ­gure 2. I n chronic myelogenic leukosis, the mean values are almost equal to those of the controls ( p > 0 . 8 ) . According to stage of the leukosis affection, the changes in immunoglobulins are characterized by the following pecu­l iar i t ies : in the early stages of the disease, the level of I g G class displays an insignificant rise in a l l three forms of leukosis (acute, chronic myelo­genic and chronic lymphatic) — p > 0 . 3 . At the onset of acute leukoses, Fhe second class IgM is significantly increased as compared to controls (182 ± ± 9 4 mg %, р<(У.01). A rise in the mean values of IgA is also found in the same type of leukoses (249+101 mg %, p<0 .05 ) . I n the early stage of chro­nic lymphatic leukosis, the serum level of IgM and IgA is reduced compared wi th the controls, wi th the difference in class IgM being si gnificant ( 9 7 ± 2 1 mg %, p<0 .01 ) . I n chronic myelogenic leukosis, the changes in serum le­vels of the three immunoglobulin classes display values close to those of the controls. I n the other stages of acute leukosis and chronic leukosis (be­fore treatment, in the course 6f treatment, after treatment and during re­lapses) no essential changes in I g G and IgA are established ( p > 0 . 3 ) . Only IgM displays a reliable reduction of its level during the evolution of the disease, mostly manifested in chronic lymphatic leukosis ( 9 5 ± 6 7 mg %, 1 164 Е. Yordanova, М. Radkov, R. Mishkova p < 0 . 0 1 ) . During recurrence, a reduction of IgA level is also established in chronic lymphatic leukosis ( 8 8 ± 3 9 mg %, p<0 .01) . Among the group of malignant lymphoblastomas, no essential change* in the three immunoglobulin classes are established* both relative to the summed up data concerning the entire group, and to the type and stage of the disease ( p > 0 . 3 — p > 0 . 9 ) . I n the reticulosis group, an in­crease of IgG is noted both at the onset of the disease, and during the relapse (p<0 .05) . The IgG se­rum level in the beginning reveals a stronger increase than during the recurrence, although the differ­ence between their mean values is insignificant ( p > 0 . 2 ) ; the other two classes — Ig'M and IgA — show no difference worth noting as compared to controls ( p > 0 . 6 ) . A more detailed discussion w i l l be made of the changes in the three immunoglobulin classes in the nine patients wi th myeloma di­sease under study, since they are characterized by a number of pe­culiarit ies. I n the myeloma di­sease, the greatest increase record­ed concerns the IgG class, both at the onset and during the recurrence of the condition (3269+1849 mg % and 4 4 8 0 ± 2 2 8 6 mg % , p < 0 . O l ) . In the other two classes — IgM and IgA — fhe changes are insig­n i f ican t in comparison wi th the controls ( p > 0 . 7 ) (F ig . 3) . Among the patients wi th myeloma, the gamma-myeloma type cases predo­minate (8 out of a total of 9 cases). The values of immunoglobulins for the three classes in the cited above patients wi th gamma-myeloma disease disclose a number of differences,: three of the patients have increased IgG and IgA values, wi th the IgA being significantly increased up to 640 mg % (p <0.01) . I n three of the patients there is a rise of the macroglobulin fraction, judged from the IgM increase. Only in one of the myeloma patients rather low IgA values are found, as well as absence of the remaining two immunoglobulin classes. The plasma levels of I gG and IgA immunoglobulins in two cases wi th myeloma, fol­lowed up in dynamics, display a considerable reduction of their mean va­lues following cytostatic therapy (p<0 .05) . The highest IgG values (5800 Fig . 3. Changes in serum immunoglobulins in myeloma disease. Study on the Serum Leveis of Immunoglobulins. . . nig % ) are recorded in one of the patients with beta myeloma. The data submitted point to the fact that in part of the myeloma patients, it is a matter of monoclonal gammapathy, and in another part — of polyclonal gammapathy. I n the group of hemorrhagic diathesis (essential thrombocytopenia and hemophilia), a reliably increased IgG value is established both at the onset of the disease, and during the relapse (p<0.01), wi th the difference between the mean immunoglobulin values in either of the cases being insignificant ( p > 0 . 0 3 ) . The other two classes — IgM and IgA — s imi la r ly do not show essential d ifference ( p > 0 . 3 ) . Among the polycythemia vera patients, cer-tain fluctuations are established in a l l three classes of immunoglobulins wi th unessential differences as compared to controls ( p > 0 . 7 ) . Interpretation of the changes in the other paraclinical indicators failed to affirm a definite interdependence between changes in their values and changes in the plasma immunoglobulins. Due to space restrictions, we are not in a position to deal more extensively with this part icular issue in the present report. T h e changes in the plasma level of immunoglobulins established among patients wi th malignant hemopathies may be classified, according to Wal -denstrom, wi th the monoclonal and polyclonal gammapathies (7). They are produced as the result of chronic stimulation of the reticuloendothelial system, invo lv ing a great number of cellular lines (clones according to the clonal-selection theory of Burnett) , wi th concomitant increase of a l l , or of a great number of the different immunoglobulin classes. I n malignant hemo-pathies, after estimating the state of humoral immunity , due consideration should be given to the corticosteriod therapy applied in many of the diseas-es. As wel l known, corticosteroids inhibit both the function of the reti-culoendothelial system, and the excess antibody production. Thus, the lower plasma level of IgM and IgA in chronic lymphatic leukosis might be explain-ed. On the other hand, the strongly pronounced increase of IgA in some malignant hemopathies may be assumed as an expression of autoimmuni-zation processes also, since it is universal ly known that IgA is a carrier of autoantibodies in the organism (8) . Conclusions ! . The level of plasma immunoglobulins from the three classes ( I g G , I g M and IgA) in malignant hemopathies shows changes of the type of mono-clonal and polyclonal gammapathies (p<6.01) . 2. I n acute leukosis, the immunoglobulins are moderately increased; in chronic lymphatic leukosis, IgM and IgA display a reduction as compar-ed to controls, and in chronic myelogenic leukosis the values of the three immunoglobulin classes prove to be close to those of the controls. 3. Among the patients w i th reticulosis, the I g G class shows a substan-t i a l increase in cases w i th myeloma, as much in the course of the disease, as in the relapse period. 1 166 Е- Yordanova, М. Radkov, R. Mishkova 4. I n the other malignant hemopathies, the changes in the mean values of the .plasma immunoglobulin levels for the three Ig classes are close to those of the controls, and do not show significant variations. R E F E R E N C E S 1. Й о p д а и о в а, Е. , M. Р а д к о в , Р . М и ш к о в а. Имунии изследвания при анемии, доклад на I I I научно-практ. конф. по хематология, Мед. ф-тет — Варна. — 2. М о н е е в а , Р . , Ф. Ф а й н ш т а й н , М. Х о х л о в а , Э. Т е р е н т ь е в а и др. Сравнительное изучение так называемой доброкачественной «моноклоновой» гаммопатии парапроетинемических ретикулезов, резюме от Мат. 44 науч. сес. ЦОЛИПК—СССР, М., 17—18, 5, 1973. — 3. Р а д к о в, М., Е. Й о р д а н о в а . Епид., микр. и инф. бол., 10, 1973, 1, 75—78. — 4. X р и с о х о, Р . Можност за широка примена на радиарната имунодифузия. Сборник на труд, от V I I I конгр. на лекарите от Македония, 2—4. 10. 1970, Охрид. — 5. B r a u n , H. J. Die Thera-piewoche, 17, 47, 1967, 1926. — 6. De B a c , C., F . A i u t i , A. C i re l l i . Boll. Soc. Ital. Biol. Sper., 40, 1964, 1977. — 7. F i n e , J . M. Rev. Prat., 18, 1968, 11, 1965—1967. — 8. F l e i c h m a n n , J . B . Ann. Rev. Biochem., 35, 1966, 835 .— 9. K l e m m , D. Med. Klinik, 61, 1966, 1835. — 10. M a n с i n i , G . , А. C a r b o-n a r a , J . H e r e m a n s . Immunochemistry, 2, 1965, 236. — 11. Mukhad-z e , M. G . I I Meeting of the European and African Division of the International So­ciety of Hematology, Prague, 27—29. 8. 1973, C S S R . — 12. N a j m a n , A . , A . G е r-b a 1, C. R o p a i r s . Nouv. Rev. d'Hemat., 11, 1971, 3, 365—371. И С С Л Е Д О В А Н И Е С Ы В О Р О Т О Ч Н Ы Х У Р О В Н Е Й И М М У Н О Г Л О Б У Л И Н О В IgG, IgM И IgA П Р И З Л О К А Ч Е С Т В Е Н Н Ы Х Г Е М О П А Т И Я Х Е. Йорданова, М. Радков, Р. Миткова Р Е З Ю М Е Чтобы проследить изменения в сывороточных у р о в н я х иммуноглобу­линов I g G , IgM и IgA при злокачественных гемопатиях, исследованы 122 больных, леченных в гематологической клинике Медицинского фа­культета — Варна , за период 1971 —1973 г. Путем метода количествен­ного определения иммуноглобулинов посредством радиальной иммуно-диффузии по Манчини прослежены 55 больных лейкозом, 31 больной, злокачественными лимфобластомами, 22 — ретикулезами, 8 — геммрра-гическими диатезами и 6 больных с истинной полицитемией. В резуль­тате исследования получены данные, которые указывают на наличие изменений в сывороточном уровне иммуноглобулинов при злокачествен­ных гемопатиях типа моноклональных и поликлональных гемопатий, лучше всего выраженных у больных лейкозами и миеломной болезнью. П р и остром лейкозе иммуноглобулины всех трех классов умеренно уве­личены, при хроническом лимфатическом лейкозе IgM и IgA —- умень­шены, а при миелогенном хроническом лейкозе устанавливаются несу­щественные изменения иммуноглобулинов. Сильное увеличение иммуно­глобулинов класса IgG устанавливается у больных миеломной болезнью, к а к во ввемя болезни, так и при рецидиве. 

STUDY ON THE SERUM LEVELS OF IMMUNOGLOBULINS lgG, igM, IgA IN MALIGNANT HEMOPATHIES

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STUDY ON THE SERUM LEVELS OF IMMUNOGLOBULINS lgG, igM, IgA IN MALIGNANT HEMOPATHIES

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