The amyotrophic lateral sclerosis and some other neuropathies without patches are caused by a re-infection (toxi-infection) from Bordetella Pertussis in subjects with astrocytes non-producers of II-class HLA-Antigens: fundamentally they all have the same pathogenesys.

In thirtyfour patients affected by amyotrophic lateral sclerosis (ALS) and in seven patients affected by other neuropathies without patches (N-PN), I have searched for anti Bordetella Pertussis (BP) antibodies by the same methodology I used for Multiple Sclerosis (MS): all of them have come out to be affected by a BP infection taking place ^{(See notes 1, 2)}. If the diseases under discussion have the same etiology (a toxi-infection by Bordetella Pertussis), how can we explain the considerable difference in the anatomic-pathologic damages?

From experimental pathology we know that ^{(See notes 3, 4, 5)} :

1. in a specific animal Species, the experimental allergic encephalitis (EAE), in its form considered the experimental model of human MS, may be induced only in breeds with astrocytes which produce II-class HLA-Antigens; it does not develop in the races with astrocytes which do not produce II-class HLA Antigens.
   
2. Anti II-class HLA-Antigens Antibodies inhibit EAS onset;
   
3. Soluble adhesive molecules (s-ICAM) are present in MS, they are not present in non-inflammatory neuropathies (included ALS).

From immunology we know that ^{(See note 6)} "the capacity of immune complexes of modifying or modulating the immune response, both humoral and cellular, is well-known , even if the intimate mechanisms that rule such processes are still mostly unknown." … "A suppression of the immune response and of the lymphocyte activation by immune complexes has been known for a long time.."..

The underlying mechanisms would be ^{(See note 6)} :

• an antigen's "concealment";
  
• a release of suppression's soluble factors by T and B lymphocytes, when their FC receptors are "held" by immune complexes ;
  
• a competition with the free antigen for surface receptor of T-lymphocytes;
  
• an indirect suppression, mediated by the activation of fractions of Complement;
  
• a "blocking" action of immune complexes on macrophages and on T-cytotoxic lymphocytes.

From microbiology we know that ^{(See note 7)} the characters of immunologic response distinguish endotoxins (Lipopolysaccharide) from other antigens: the response expresses an IgM prolonged synthesis, sometimes in total absence of IgG (contrary to what usually happens with other antigens); the rates of these macroglobulins (IgM) vary in a cyclic way due to a phenomenon of back-control, for which the antigen-antibody complexes that are formed inhibit the further immune response. If the antigen endures enough time in the host, a new cycle of antibody synthesis may be produced.

As a matter of fact, when the immune circulating complexes reach a sufficiently high level, they inhibit the antibody production; for a certain period no other immune complexes are formed . The ones already formed (circulating), caught by the Reticuloendothelial System, are little by little eliminated (the inhibitory effect ceases). In the chronic infections (protracted passage of toxins in circulation), once the inhibitory effect by ICC has ceased, the production of new antibodies and the formation of new ICC start again, we come to a new inhibition of antibody production.

These cycles go on recurring till the toxin production lasts (till the infection lasts). To the questions we were asked, we may answer that: The early pathogenic mechanisms (pertussis reinfection in subject with a muco-ciliar barrier defect, BP toxin passage in circulation, immune circulating complexes formation) are the same described for MS ^{(See notes 1-2)}. In the two categories of neuropathies (with patches or without patches) it is the astrocytes' and ICC's roles (ICC form in all cases) that makes the difference:

• In MS, the astrocytes are producers of II-class HLA-Antigens, and make the endothelia expose adhesion molecules. ICC, "kept" by adhesion molecules, precipitate in the CNS; in circulation, as a rule, they do not reach such high concentrations to become inhibitory.
• In ALS and in other non-patched neuropathies (NPN) astrocytes are not producers of II-class HLA-Antigens; the endothelia of cerebral vessels do not expose adhesion molecules. Among immune complexes, the ones which form in the zone of equivalence precipitate in the rhino-sinal mucosa (Arthus Phenomenon); the ones which form in an excess of antigen or in an excess of antibodies (practically, the most part) go on circulating in the blood till they are kept and destroyed by the Reticuloendothelial System (Spleen and Liver). The persistence in circulation of most part of ICC which form, leads to their progressive increase, so that in the end spring the inhibitory mechanisms that ICC themselves trigger off in the production of antibodies. In chronic pertussis infections in subjects with astrocytes non-producers of II-class HLA-Antigens, during the inhibiting phases from immune complexes (relative lack of antibodies), the BP toxins which go into blood fix them directly on neuroepithelia: we have neuropathies without patches. The pathogenic power of the various pertussis toxins ^{(See notes 1-2)} perfectly explains the neuroepithelial damages characteristic of the neuropathies without patches.

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