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On the possibility of preventing multiple sclerosis
Medical Hypotheses (1998)51, 445-446
© HarcourtBrace& Co. Ltd 1998
Short Note: On the possibility of preventing multiple sclerosis T. MARCINKOWSKI Chair and Department of Forensic Medicine, Pomeranian Academy of Medicine, Szczecin, Poland. Correspondence to: Tadeusz Marcinkowski, Zak~ad Medycyny S~lowej PAM, al. Powstahcdw Wlkp, 72, 70-111 Szczecin, Poland
Abstract - - The role of immune complexes in the etiology and pathogenesis of demyelinating diseases, particularly multiple Sclerosis, is discussed in the light of numerous observations. It is inferred that a deeper understanding of the role of immune complexes might provide a basis for preventive measures in multiple sclerosis.
Immune complexes appear in the blood in the presence of various antigens or haptens which enter the organism following such events as infection or venopuncture. A classic example of the latter route is the transfusion of unmatched blood. However, inhaled air containing dust-borne aphthoid fungi, fragments of hair, human secretions or excretions (e.g. sweat, tears, saliva, urine or sperm) provides a hitherto unappreciated source of antigen for the formation of immune complexes. The inhalatory route can be active over long periods of time, particularly in indoor spaces where ventilation is limited. The mechanism by which inhaled air supplies antigens for the formation of immune complexes may well be seen using anti-H antibodies as an example. These irregular antibodies are found in the serum of some individuals of the A1B blood group (1), who in consequence are sensitized to antigen H. Antigen H is present on the surface of erythrocytes of the O blood group. In many individuals (secretors) of the O blood group population antigen H is found also in body fluids and is released with exhaled air. It may well be possible that the presence of a secretor near a
sensitized individual eventually elicits an immune reaction in the latter whose blood now contains multimolecular hydrophobic complexes of antibody (anti-H) with inhaled antigen H. Depending on the molar concentration of antibody and antigen the complexes are soluble or precipitate. The highest titre of antigen H is found in saliva and sperm (1:256 to 1:1024), while in tears the titre is relatively low (1:2 to 1:8). This large range of titres is reflected in varying amounts of the antigen entering the blood of a sensitized individual which at some point may be optimal for precipitation. Precipitating immune complexes, usually larger than 19S, trigger further reactions typical of serological conflict, like dilatation of vessels, increase in vascular permeability, binding of complement, release of hormones and mediators, etc. A part of the precipitating complexes is deposited under the endothelium but some of them damage the blood-brain barrier and permeate into the central nervous system. We infer that plaques typically found in multiple sclerosis (MS) but also in postvaccinal encephalitis and similar conditions (2--4) are immune complexes
Received 11 March 1997 Accepted 14 May 1997 445
446 that have passed the blood-brain barrier. In the case of MS, some if not all complexes could have formed after inhalation of a foreign antigen. Consequently, the identification and removal of sources of airborne antigen might be an important preventive measure in MS. Attention should not be limited to plants and animals. The example of antigen H demonstrates the importance of human sources, in particular secretors of ABH antigens. The preventive value of fresh air, through frequent and adequate ventilation, should not be underestimated. The incidence of MS in Gypsies, living almost exclusively outdoors, is extremely low. In 1990 Bisgard from Denmark (5) studied the seasonal appearance of MS in 45 patients and found 76% of exacerbations in winter. The incidence of the disease is greater in colder regions of the world and among individuals living in crowded indoor areas (2,6--9). Preventive measures should not be limited to ventilation, however. Let us consider the fact that MS often effects young persons at the start of their marital life. Couples have been reported with strong links between both partners yet with one of them feeling distinctly uncomfortable or having overt symptoms of disease (headache, vertigo, syncope, etc.) in the presence of the other. Not finding any cause of disease, such persons should be advised to sleep in separate rooms.
MEDICAL HYPOTHESES
Serological tests might be helpful in disclosing the underlying immunological conflict. In conclusion, the evidence that MS is a form of immunological disease should be given due attention. Preventive measures aimed at removing the source of antigen should be contemplated in each case. References 1. Krug S. [Morphological basis of diseases of the nervous system]. In: Krug S, Skrzypek-Fakhoury E, eds. [Clinical Pathomorphology], Warsaw: PZWL, 1966:789--824 2. Ironside J W. Central and peripheral nervous systems. In: Underwood J C E, ed. General and Systematic Pathology. Edinburgh: Churchill Livingstone, 1992: 747-802. 3. Marcinkowski T. The diseases of Alzheimer and Pick from the viewpoint of prevention. Med Hypotheses 1996; 46: 180-182. 4. Marcinkowski T. [Circulating Immune Complexes and their Role in Some Pathologic Processes]. Szczecin, Poland: hydawnictwo Promocyine Albatros, 1996. 5. Bisgard C. Seasonal variation in disseminated sclerosis. Ugeskr Laeger 1990; 152(16): 1160--1161. 6. Bannister R. [Clinical Neurology]. Bielsko-BiaPa, Poland: Alpha-medica Press, 1995. 7. Cendrowski W S. [Disseminated Sclerosis], 2nd end. Warsaw: PZWL, 1993. 8. Gabryel P, Szyma~ J. [Pathology of the nervous system]. In: Groniowski J, Kru~ S, eds. [Basic Pathomorphology]. Warsaw: PZWL, 1991: 782-809. 9. Jakimowicz W. [An Outline of Clinical Neurology], Warsaw: PZWL, 1987.
© HarcourtBrace& Co. Ltd 1998
Short Note: On the possibility of preventing multiple sclerosis T. MARCINKOWSKI Chair and Department of Forensic Medicine, Pomeranian Academy of Medicine, Szczecin, Poland. Correspondence to: Tadeusz Marcinkowski, Zak~ad Medycyny S~lowej PAM, al. Powstahcdw Wlkp, 72, 70-111 Szczecin, Poland
Abstract - - The role of immune complexes in the etiology and pathogenesis of demyelinating diseases, particularly multiple Sclerosis, is discussed in the light of numerous observations. It is inferred that a deeper understanding of the role of immune complexes might provide a basis for preventive measures in multiple sclerosis.
Immune complexes appear in the blood in the presence of various antigens or haptens which enter the organism following such events as infection or venopuncture. A classic example of the latter route is the transfusion of unmatched blood. However, inhaled air containing dust-borne aphthoid fungi, fragments of hair, human secretions or excretions (e.g. sweat, tears, saliva, urine or sperm) provides a hitherto unappreciated source of antigen for the formation of immune complexes. The inhalatory route can be active over long periods of time, particularly in indoor spaces where ventilation is limited. The mechanism by which inhaled air supplies antigens for the formation of immune complexes may well be seen using anti-H antibodies as an example. These irregular antibodies are found in the serum of some individuals of the A1B blood group (1), who in consequence are sensitized to antigen H. Antigen H is present on the surface of erythrocytes of the O blood group. In many individuals (secretors) of the O blood group population antigen H is found also in body fluids and is released with exhaled air. It may well be possible that the presence of a secretor near a
sensitized individual eventually elicits an immune reaction in the latter whose blood now contains multimolecular hydrophobic complexes of antibody (anti-H) with inhaled antigen H. Depending on the molar concentration of antibody and antigen the complexes are soluble or precipitate. The highest titre of antigen H is found in saliva and sperm (1:256 to 1:1024), while in tears the titre is relatively low (1:2 to 1:8). This large range of titres is reflected in varying amounts of the antigen entering the blood of a sensitized individual which at some point may be optimal for precipitation. Precipitating immune complexes, usually larger than 19S, trigger further reactions typical of serological conflict, like dilatation of vessels, increase in vascular permeability, binding of complement, release of hormones and mediators, etc. A part of the precipitating complexes is deposited under the endothelium but some of them damage the blood-brain barrier and permeate into the central nervous system. We infer that plaques typically found in multiple sclerosis (MS) but also in postvaccinal encephalitis and similar conditions (2--4) are immune complexes
Received 11 March 1997 Accepted 14 May 1997 445
446 that have passed the blood-brain barrier. In the case of MS, some if not all complexes could have formed after inhalation of a foreign antigen. Consequently, the identification and removal of sources of airborne antigen might be an important preventive measure in MS. Attention should not be limited to plants and animals. The example of antigen H demonstrates the importance of human sources, in particular secretors of ABH antigens. The preventive value of fresh air, through frequent and adequate ventilation, should not be underestimated. The incidence of MS in Gypsies, living almost exclusively outdoors, is extremely low. In 1990 Bisgard from Denmark (5) studied the seasonal appearance of MS in 45 patients and found 76% of exacerbations in winter. The incidence of the disease is greater in colder regions of the world and among individuals living in crowded indoor areas (2,6--9). Preventive measures should not be limited to ventilation, however. Let us consider the fact that MS often effects young persons at the start of their marital life. Couples have been reported with strong links between both partners yet with one of them feeling distinctly uncomfortable or having overt symptoms of disease (headache, vertigo, syncope, etc.) in the presence of the other. Not finding any cause of disease, such persons should be advised to sleep in separate rooms.
MEDICAL HYPOTHESES
Serological tests might be helpful in disclosing the underlying immunological conflict. In conclusion, the evidence that MS is a form of immunological disease should be given due attention. Preventive measures aimed at removing the source of antigen should be contemplated in each case. References 1. Krug S. [Morphological basis of diseases of the nervous system]. In: Krug S, Skrzypek-Fakhoury E, eds. [Clinical Pathomorphology], Warsaw: PZWL, 1966:789--824 2. Ironside J W. Central and peripheral nervous systems. In: Underwood J C E, ed. General and Systematic Pathology. Edinburgh: Churchill Livingstone, 1992: 747-802. 3. Marcinkowski T. The diseases of Alzheimer and Pick from the viewpoint of prevention. Med Hypotheses 1996; 46: 180-182. 4. Marcinkowski T. [Circulating Immune Complexes and their Role in Some Pathologic Processes]. Szczecin, Poland: hydawnictwo Promocyine Albatros, 1996. 5. Bisgard C. Seasonal variation in disseminated sclerosis. Ugeskr Laeger 1990; 152(16): 1160--1161. 6. Bannister R. [Clinical Neurology]. Bielsko-BiaPa, Poland: Alpha-medica Press, 1995. 7. Cendrowski W S. [Disseminated Sclerosis], 2nd end. Warsaw: PZWL, 1993. 8. Gabryel P, Szyma~ J. [Pathology of the nervous system]. In: Groniowski J, Kru~ S, eds. [Basic Pathomorphology]. Warsaw: PZWL, 1991: 782-809. 9. Jakimowicz W. [An Outline of Clinical Neurology], Warsaw: PZWL, 1987.