- Email: [email protected]
Circulating soluble adhesion molecules: more observations on ICAM-1 in patients with Hodgkin's disease
kaleidoscope lei-÷crs Is malaria linked to the absence of a-galactosyl epitopes in Old World primates? In an interesting viewpoint article I, Uri Galili discusses the significance to xenotransplantation in humans of the absence of Galal-3Gall~ 1-4G!cNAc-R structures (termed the a-galactosyl epitope) and the corresponding appearance of natural (anti-Gal) antibodies in humans. Nonprimate mammals and New World monkeys express the a-galactosyl epitope and have no anti-Gal antibodiesL Galili suggests that selective pressure exerted by a pathogen endemic to the Old World might have resulted in the inactivation of the a 1,3 galactosyltransferase (a 1,3GT) gene, which synthesizes a-galactosyl epitopes. Thus, Old World primates may have developed a defensive mechanism against the pathogens thrr, ugh the loss of immune tolerance ana the production of anti-Gal antibodiesL
There is evidence to suggest that the malaria parasite may be the pathogen responsible for this selective pressure2. Primate malaria is endemic in the Old World and is believed to have been introduced to the New World during the time of Christopher Columbus. Malaria is known to have exerted selective pressure on human populations at the level of globin and human major histocompatibility complex (MHC) HLA genes 3"4. The human malaria parasite Plasrnodi,tm falciparum expresses terminal a-linked galactose in glycoproteinss, which is recognized by antibodies in normal-' and immune 6 human sera. Clearly however, the level; of natural anti-Gal antibodies in human plasma do not provide complete protection from infection with any of the four human malaria parasites, including P. falciparum. On the other hand, P. falciparum readily infects certain New World monkeys, but not Old World monkeys~. It will be interesting to determine if P. falciparum growth
in vitro is influenced by anti-Gal antibodies, and whether or not other parasite species that infect Old World primates contain agalactosyl epitopes.
RanjanRamasamy Division of Life Sciences, Institute of Fundamental Studies, Hantana Road, Kandy, Sri Lanka. References 1 Galili, U. (1993) lmmunol. Today 14, 480-482 2 Ramasamy, R. (1988) IndianJ. Med. Res. 87, 584-593 3 Allison, A.C. (1954) Trans. R. Soc. Tr@. Med. Hyg. 48, 312-318 4 Hill, AN.S, Allsopp, C.E.M., Kwiatkowski, D. et al. (1991) Nature 352, 595-600 5 Ramasamy, R. and Reese, R.T. (1986) Mol. Biocbem. Parasitol. 19, 91-101 6 Ramasamy, R. and Reese, R.T. (1985)J. lmmunol. 134, 1952-1955 7 Collins, W.E. (1992) Mere. Ist. Oswaldo C~ez 87, 401-406
Circulating soluble adhesion molecules: more observations on the increased levels in disease In the October issue of Immunology Today, Andrew Gearing and Walter Newman reviewed the mo.ny recent findings that demonstrate increased levels of various members of the selectin and immunoglobulin superfamilies in different disease states. Furthermore, they suggest that these increases l , ay provide a useful means of monitoring disease progression. This review has generated much interest and two items of the correspondence that has been received by Immunology Today follow. In the first letter, Giovanni Pizzolo et al. describe the increase of soluble intercellular adhesion molecule 1 (slCAM-1) in Hodgldn's disease and discuss how this may play a role in the pathophysiology of the disease. In the sccond letter, Stephan Martin et al. suggest that the increase in soluble adhesion receptors may play a prot~ective role in autoimmunity, particularly in individuals who do not demonstrate an increased risk of developing type I diabetes, but who do represent a genetic risk.
Circulating soluble ICAM-1 in patients with Hodgkin's disease In a recevr article in Immunology "loday, Gearing and Newman provided an exhaustive overview of the disease states in which increased levels of circulating soluble adhesion molecules have been detected, and discussed
the issue of their possible physio logical relevance 1. However, they did not mention a number of recent studies relating to the level of circulating soluble intercellular adhesion molecule i (sICAM-i) in Hodgkin's disease (HD) (Refs 2-4), as these data only became available while their review was in press, Therefore, to add to this review, we wo,ld like to summarize and briefly comment on these new data.
r-.,,u,ologrtoday
140
We investigated ICAM-1 tissue imm.unoreactivity and serum levels of slCAM-I in adult patients presenting with HD. The ICAM-1 molecule was found to be expressed strongly in tissues i~volved in the disease, and serum levels of slCAM-1 were higher in HD patients (79 cases) than in normal controls (538+235 versus 399_+!_28ng ml-~; p<0.01). Levels of sICAM-1 were also higher in patients with more-advanced HD
Vot. 15 No. 3 1994
kaleidoscope letters (stages III and IV) than in patients with ~ess-advanced disease (stages I and II) (646+236 versus 479+214 ng ml-~; P=0.002); in patients with stage 'B' compared with stage 'A' disease (675+228 versus 459_+202 ng ml-*; p<0.0001); and in patients with 'bulky' compared with 'non-bulky' disease (622_+240 versus 504+226 ngm]-~; P--0.042). Similar data have been reported recently in two other studies, which demonstrate that serum levels of slCAM-1 are increased in patients with HD and correlate positively with disease stage and activity both in adults 3 and in chiidren 4. The increased levels of circulating slCAM-I may play a pathophysiological role in the irregularities of the immune system that are usually found in patients with HD, by competing with tissue ICAM-1 during cell--cell adhesionk The overexpression of tissue ICAM-1 is consistent with an excess of binding sites for lymphocyte functionassociated molecule 1 (LFA-1) molecules present on T cells. This
A physiological role for c!rcmaung adhesion molerules?
could account for the lymphocyteGianpaolo Nadali homing abnormalities observed in Marco Chilosi HD, i.e. the preferential tissue accumulation of CD4 ÷ T Ivmpho- Depts of Haematology and Pathology, cytes associated w~A : ~ ; partial Verona University School of depletion from peripheral blood. Medicine, The overexpression of tissue Verona, Italy. ICAM-1 also leads to the release and accumulation of slCAM-1 in Gianpietro Semenzato the serum. Since slCAM-1 retains the ability to bind specifically to Dept of Clinical Medicine, LFA-I (Ref. 5~, its excess in HD is Padova University School of likely to saturate the membrane Medicine, LFA-1 on circulating T cells that Padova, Italy. escape from the tissue, thereby affecting their adhesion poteatial References and function. We suggest that in 1 Gearing, A.J.H. and Newman, W. HD the overexpression of tissue (1993) Immunol. Today 14, ICAM-1 that le As to an increase in 506-512 circulating slCAM-1 may interfere 2 Pizzolo, G., Vinante, F., Nadali, G. with the lymphocyte adhesion et al. (1993) Br. J. Haematol. 84, machinery, and contribute to the 161-162 well-known anomalies observed in 3 Gruss, H-J., Do!ken, G., Brach, M.A., Mertelsmann, R. and the immune systems of these Herrmann, F. (1993) Leukemia 7, patients. This mechanism may not 1245-1249 only take place in HD, but also m 4 Pui, C-H., Luo, X., Evans, W. et al. other neoplastic conditions. (1993) Blood 82, 895-898 5 Rothlein, R., Mainolfi, E.A., Giovanni Pizzolo Czajkowski, M., Marlin, S.D. (1991) Fabrizio Vinante J. !mmunol. 147, 3788-3793
major histocompatibility complex Ilia
rvn~g l-)R~i ~ncl/c~r D R 4 wirh
the diabetic family member. Thus, elevated cL-selectin and clCAM-1 levels occurred in individuals who In a recent review of circulat- did not demonstrate an increased ing adhesion molecules 1, Andrew risk of developing type 1 diabetes Gearing and Walter Newman over- (i.e. no islet autoantibodies), but looked a paper that presents data who did have a genetic risk. We favouring a protective role for so!- assume that circulating adhesion uble adhesion receptors in auto- molecules may have protected these immunityz. This paprr r,*ptesents the individuals from developing islet first description of elevated levels autoimmunity. Indeed, in a more recen.~ study, of circulating L-selectin (cL-selectin we have found in vitro evidence and circulating intercellular ad hesion molecule 1 (cICAM-1) in an that physiological levels of soluble autoimmune disease (type 1 dia- iCAM-1 can interfere with the actibetes), and also demonstrates the vation of islet-reactive autoimmune presence of elevated levels of these T cells (B.O. Roep et al., unpubadhesion receptors in first de~ree lished). Normal levels of cL-selectin relatives of diabetic patien:s. impair lymphocyte adhesion to Surprisingly, elevated levels weJe endothelial cells3. Taken together, not only observed in relatives with these data imply that circulating antibodies to islet cells (i.e. with a adhesion molecules have immunohigh risk of diabetes), but also in a modulatory functions. Andrew Gearing and Walter small number of relatives without such antibodies. This proportion of Newman use the prefix 's' to describe relatives who were low-risk for soluble recombinant and natural diabetes shared the diabetes-associated circulating adhesion molecules. In
Imm..otogy roaay
141
those cases where the identity of the two forms has not been established, we suggest that they should be distinguished as soluble (s) and circulating (c) forms, as has been described previously4. Stephan Martin Eberhard F. Lampeter Hubert Kolb
Diabetes Research Institute at the Heinrich-Heine- University Diisse!dor[, Clinical Depar~.ment, Auf'm l-!ennekamp 65, 4022S Diisseldorf, Germany. References 1 Gearing, A.J.H. and Newman, W. (1993) Immunol. Today 14, 506-512 2 Lampeter, E.F., Kolb, H., Mainolfi, E.A. et al. (1992) Diabetes 41, 1668-1671 3 Schleiffenbaum,B., Spertini, O. and Tedder, T.F. (1992)J. Cell Biol. 119, 229-238 4 Rothlein, R., Mainolfi, E.A., Czajkowski, M. and Marlin, S.D. (1991) J. Immunol. 147, 3788-3793
Vol. 15 No. 3 1994
There is evidence to suggest that the malaria parasite may be the pathogen responsible for this selective pressure2. Primate malaria is endemic in the Old World and is believed to have been introduced to the New World during the time of Christopher Columbus. Malaria is known to have exerted selective pressure on human populations at the level of globin and human major histocompatibility complex (MHC) HLA genes 3"4. The human malaria parasite Plasrnodi,tm falciparum expresses terminal a-linked galactose in glycoproteinss, which is recognized by antibodies in normal-' and immune 6 human sera. Clearly however, the level; of natural anti-Gal antibodies in human plasma do not provide complete protection from infection with any of the four human malaria parasites, including P. falciparum. On the other hand, P. falciparum readily infects certain New World monkeys, but not Old World monkeys~. It will be interesting to determine if P. falciparum growth
in vitro is influenced by anti-Gal antibodies, and whether or not other parasite species that infect Old World primates contain agalactosyl epitopes.
RanjanRamasamy Division of Life Sciences, Institute of Fundamental Studies, Hantana Road, Kandy, Sri Lanka. References 1 Galili, U. (1993) lmmunol. Today 14, 480-482 2 Ramasamy, R. (1988) IndianJ. Med. Res. 87, 584-593 3 Allison, A.C. (1954) Trans. R. Soc. Tr@. Med. Hyg. 48, 312-318 4 Hill, AN.S, Allsopp, C.E.M., Kwiatkowski, D. et al. (1991) Nature 352, 595-600 5 Ramasamy, R. and Reese, R.T. (1986) Mol. Biocbem. Parasitol. 19, 91-101 6 Ramasamy, R. and Reese, R.T. (1985)J. lmmunol. 134, 1952-1955 7 Collins, W.E. (1992) Mere. Ist. Oswaldo C~ez 87, 401-406
Circulating soluble adhesion molecules: more observations on the increased levels in disease In the October issue of Immunology Today, Andrew Gearing and Walter Newman reviewed the mo.ny recent findings that demonstrate increased levels of various members of the selectin and immunoglobulin superfamilies in different disease states. Furthermore, they suggest that these increases l , ay provide a useful means of monitoring disease progression. This review has generated much interest and two items of the correspondence that has been received by Immunology Today follow. In the first letter, Giovanni Pizzolo et al. describe the increase of soluble intercellular adhesion molecule 1 (slCAM-1) in Hodgldn's disease and discuss how this may play a role in the pathophysiology of the disease. In the sccond letter, Stephan Martin et al. suggest that the increase in soluble adhesion receptors may play a prot~ective role in autoimmunity, particularly in individuals who do not demonstrate an increased risk of developing type I diabetes, but who do represent a genetic risk.
Circulating soluble ICAM-1 in patients with Hodgkin's disease In a recevr article in Immunology "loday, Gearing and Newman provided an exhaustive overview of the disease states in which increased levels of circulating soluble adhesion molecules have been detected, and discussed
the issue of their possible physio logical relevance 1. However, they did not mention a number of recent studies relating to the level of circulating soluble intercellular adhesion molecule i (sICAM-i) in Hodgkin's disease (HD) (Refs 2-4), as these data only became available while their review was in press, Therefore, to add to this review, we wo,ld like to summarize and briefly comment on these new data.
r-.,,u,ologrtoday
140
We investigated ICAM-1 tissue imm.unoreactivity and serum levels of slCAM-I in adult patients presenting with HD. The ICAM-1 molecule was found to be expressed strongly in tissues i~volved in the disease, and serum levels of slCAM-1 were higher in HD patients (79 cases) than in normal controls (538+235 versus 399_+!_28ng ml-~; p<0.01). Levels of sICAM-1 were also higher in patients with more-advanced HD
Vot. 15 No. 3 1994
kaleidoscope letters (stages III and IV) than in patients with ~ess-advanced disease (stages I and II) (646+236 versus 479+214 ng ml-~; P=0.002); in patients with stage 'B' compared with stage 'A' disease (675+228 versus 459_+202 ng ml-*; p<0.0001); and in patients with 'bulky' compared with 'non-bulky' disease (622_+240 versus 504+226 ngm]-~; P--0.042). Similar data have been reported recently in two other studies, which demonstrate that serum levels of slCAM-1 are increased in patients with HD and correlate positively with disease stage and activity both in adults 3 and in chiidren 4. The increased levels of circulating slCAM-I may play a pathophysiological role in the irregularities of the immune system that are usually found in patients with HD, by competing with tissue ICAM-1 during cell--cell adhesionk The overexpression of tissue ICAM-1 is consistent with an excess of binding sites for lymphocyte functionassociated molecule 1 (LFA-1) molecules present on T cells. This
A physiological role for c!rcmaung adhesion molerules?
could account for the lymphocyteGianpaolo Nadali homing abnormalities observed in Marco Chilosi HD, i.e. the preferential tissue accumulation of CD4 ÷ T Ivmpho- Depts of Haematology and Pathology, cytes associated w~A : ~ ; partial Verona University School of depletion from peripheral blood. Medicine, The overexpression of tissue Verona, Italy. ICAM-1 also leads to the release and accumulation of slCAM-1 in Gianpietro Semenzato the serum. Since slCAM-1 retains the ability to bind specifically to Dept of Clinical Medicine, LFA-I (Ref. 5~, its excess in HD is Padova University School of likely to saturate the membrane Medicine, LFA-1 on circulating T cells that Padova, Italy. escape from the tissue, thereby affecting their adhesion poteatial References and function. We suggest that in 1 Gearing, A.J.H. and Newman, W. HD the overexpression of tissue (1993) Immunol. Today 14, ICAM-1 that le As to an increase in 506-512 circulating slCAM-1 may interfere 2 Pizzolo, G., Vinante, F., Nadali, G. with the lymphocyte adhesion et al. (1993) Br. J. Haematol. 84, machinery, and contribute to the 161-162 well-known anomalies observed in 3 Gruss, H-J., Do!ken, G., Brach, M.A., Mertelsmann, R. and the immune systems of these Herrmann, F. (1993) Leukemia 7, patients. This mechanism may not 1245-1249 only take place in HD, but also m 4 Pui, C-H., Luo, X., Evans, W. et al. other neoplastic conditions. (1993) Blood 82, 895-898 5 Rothlein, R., Mainolfi, E.A., Giovanni Pizzolo Czajkowski, M., Marlin, S.D. (1991) Fabrizio Vinante J. !mmunol. 147, 3788-3793
major histocompatibility complex Ilia
rvn~g l-)R~i ~ncl/c~r D R 4 wirh
the diabetic family member. Thus, elevated cL-selectin and clCAM-1 levels occurred in individuals who In a recent review of circulat- did not demonstrate an increased ing adhesion molecules 1, Andrew risk of developing type 1 diabetes Gearing and Walter Newman over- (i.e. no islet autoantibodies), but looked a paper that presents data who did have a genetic risk. We favouring a protective role for so!- assume that circulating adhesion uble adhesion receptors in auto- molecules may have protected these immunityz. This paprr r,*ptesents the individuals from developing islet first description of elevated levels autoimmunity. Indeed, in a more recen.~ study, of circulating L-selectin (cL-selectin we have found in vitro evidence and circulating intercellular ad hesion molecule 1 (cICAM-1) in an that physiological levels of soluble autoimmune disease (type 1 dia- iCAM-1 can interfere with the actibetes), and also demonstrates the vation of islet-reactive autoimmune presence of elevated levels of these T cells (B.O. Roep et al., unpubadhesion receptors in first de~ree lished). Normal levels of cL-selectin relatives of diabetic patien:s. impair lymphocyte adhesion to Surprisingly, elevated levels weJe endothelial cells3. Taken together, not only observed in relatives with these data imply that circulating antibodies to islet cells (i.e. with a adhesion molecules have immunohigh risk of diabetes), but also in a modulatory functions. Andrew Gearing and Walter small number of relatives without such antibodies. This proportion of Newman use the prefix 's' to describe relatives who were low-risk for soluble recombinant and natural diabetes shared the diabetes-associated circulating adhesion molecules. In
Imm..otogy roaay
141
those cases where the identity of the two forms has not been established, we suggest that they should be distinguished as soluble (s) and circulating (c) forms, as has been described previously4. Stephan Martin Eberhard F. Lampeter Hubert Kolb
Diabetes Research Institute at the Heinrich-Heine- University Diisse!dor[, Clinical Depar~.ment, Auf'm l-!ennekamp 65, 4022S Diisseldorf, Germany. References 1 Gearing, A.J.H. and Newman, W. (1993) Immunol. Today 14, 506-512 2 Lampeter, E.F., Kolb, H., Mainolfi, E.A. et al. (1992) Diabetes 41, 1668-1671 3 Schleiffenbaum,B., Spertini, O. and Tedder, T.F. (1992)J. Cell Biol. 119, 229-238 4 Rothlein, R., Mainolfi, E.A., Czajkowski, M. and Marlin, S.D. (1991) J. Immunol. 147, 3788-3793
Vol. 15 No. 3 1994