- Email: [email protected]
Immune reactivity to human recombinant Hsp-70 in subjects allergic to mite
S232 A b s t r a c t s
j ALLERGY CLIN IMMUNOL JANUARY 2002
701 AIncrease New Parameter of the Tumor Lysis Syndrome: Marked in Serum IgM M-Component in Two Patients With
,~a,~ Immune Reactivity to Human Recombinant Hsp-TO in Subjects qJl~JI Allergic to Mite
Waldenstr6m's Macroglobulinemia (WM) Treated With 2Chlorodeoxyadenosine(Cladribine)
Claudia Afferni, Bianca Barletta, Cinzia Butteroni, Patrizia lacovacci, Raffaella Tinghino, Gabriella Di Felice, Carlo Pini Institute Superiore di
Vandana M Krishna, Kurt J Bloch, Robert W Carey Massachusetts General Hospital, Boston, MA Tumor lysis syndrome (TLS) results from the rapid release of intracellular constituents into the circulation during tumor treatment. This release may result in hyperkalemia, hypercalcemia, hyperuricemia, and hyperphosphatemia. These abnormalities, in turn, may lead to life-threatening illness. TLS is associated with the treatment of leukemias, high-grade lymphomas, multiple myeloma and solid tumors. We observed two patients with WM who experienced a marked increase in their serum IgM M-component after treatment with 2-chlordeoxyadenosine (2-CDA). 2-CDA is a deoxyadenosine purine nucleoside analogue, which inhibits DNA synthesis and repair in actively dividing, as well as quiescent, cells. The major adverse effects of 2-CDA treatment axe myelosuppression and immunosuppression. TLS has been reported following treatment with 2-CDA. The bone marrow of one such patient showed necrosis of lymphoeytes. In our two patients, there was a marked increase in the concentration of the serum IgM soon after the first chemotherapy cycle was completed. The levels of serum IgM increased from 2580 mg/dL to 5900 mg/dL (relative viscosity 3.7) in the first patient and from 2360 mg/dL to 3600 mg/dL (relative viscosity 2.3) in the second patient. After the peak serum level of IgM was reached during the first treatment cycle, there was a steady decrease in concentration of IgM in both cases. Although neither of our patients experienced the hyperviscosity syndrome during treatment, the potential for this complication exists in patients with WM and higher levels of IgM before treatment. Release of large amounts of IgM M-component may constitute an additional element of TLS. Thus, patients with markedly elevated IgM concentration before treatment should be considered for plasmapheresis in anticipation of the rapid rise in IgM after chemotherapy.
Sanith, Rome, Italy The presence in nonatopic as well as allergic subjects of lgG antibodies specific for mite allergens is a well known evidence, but their physiological role in the allergic pathology is not completely understood. A recombinant allergen from Dermatophagoidesfarinae, named Mag 29, with a significant sequence homology to the caxboxyl-terminal region of the human cognate Hsp70, has been described, but is not known if patients' sera also react to human Hsp70. We detected IgG antibodies specific to recombinant human HSP-70, in sera from all the mite allergic tested, as well as from a group of nonatopic subjects, but we were not able to detect any specific IgE binding to this molecule. Moreover, we detected by ELISA and immunoblotting tecniques in the Dermatophagoidesfarinae extract a component of about 70 kDa, recognized by the IgG of the subjects tested and by a monoclonal antibody raised against Hsp-70 from bovine brain. The reactivity of this monoclonal antibody seemed to be highly cross-reactive, since it was able to bound a component of about 70 kDa in heterogeneous allergenic extracts, such as shrimp and peanut allergenic extracts, as well as in two human cellulax extracts, respectively one from peripheral blood lymphocytes and the other from a tumor epithelial cellular line. From these preliminary results, we may infer that IgG antibodies from allergic and nonatopic subjects specific for the human Hsp-70 could be cross-reactive with the component of about 70 kDa present in the crude extract of Dermatophagoidesfarinae, and also in several not-related allergenic extracts sharing antigenic epitopes with the human protein. The results of this study could be useful to understand the physiological role of the IgG antibodies specific to allergens, frequently detected both in allergic and in nonatopic subjects, in a peculiar case in which they recognize an allergenic epitope shared with self-determinants.
7 f~al'~ Abnormal Measles Serology and Autoimmunityin Autistic ChilIJIL- dren Vijendra K Singh, Courtney Nelson Utah State University, Logan, UT Immune factors such as autoimmunity may play a causal role in autism. We recently showed that many autistic children have autoantibodies to brain myelin basic protein (MBP) as well as elevated levels of measles virus antibodies. To extend this research further, we conducted a serological study of measles virus (MV), mumps virus (MuV), rubella virus (RV), cytomegalovirus (CMV), human herpesvirus-6 (HHV-6), measles-mumpsrubella (MMR), diptheria-pertussis-tetanus (DPT), diptheria-tetanus (DT) and hepatitis B (Hep B) and studied correlations with MBP autoantibodies. Antibodies were assayed in sera of autistic children (n=125) and normal children (n=92) by ELISA or immunoblotting methods. We found that autistic children have significantly (p=0.001) higher than normal levels of MV and MMR antibodies whereas the antibody levels of MuV, RV, CMV, HHV-6, DPT, DT or Hep B did not significantly differ between autistic and normal children. Immunoblotting analysis showed the presence of an unusual MMR antibody in 60% (75 of 125) of autistic children, but none of the 92 normal children had this antibody. Moreover, by using MMR blots and monoclonal antibodies, we found that the specific increase of MV antibodies or MMR antibodies was related to measles hemagglutinin antigen (MV-HA), but not to mumps or rubella viral proteins, of the MMR vaccine. In addition, over 90% of M M R antibody-positive autistic sera were also positive for MBP autoantibodies, suggesting a causal association between MMR and brain autoimmunity in autism. Stemming from this evidence, we suggest that an "atypical" measles infection in the absence of a rash but with neurological symptoms might be etiologically linked to autoimmunity in autism. (Supported by grants from the James Dougherty Jr Foundation, Unanue Foundation, Lettner Jr Foundation, Autism Autoimmunity Project and Autism Research Institute)
irma The Importance of Specific IgG. IgA and IcE to GaI-1 in Autoim~P'I' mune and Infectious Uveitis Marta Delia Romero-Piffiguer*, Juan Carlos Mui~o*, Mercedes Ferrero*, Claudio P Juarez§, Jos~ D Luna§, Gabriel Rabinovich¥ *Misericordia Hospital, C6rdoba, Argentina §Fundaci6n VER, C6rdoba, Argentina ¥Hospital Nacional de Clinicas Gral San Martin, Buenos Aires, Argentina In a previous work we described and characterized the presence of 16kDa galectin in chicken retina. The precise functions of the retinal galectin remain unknown. In previous studies we demonstrated specific IgG and IgE auto-antibodies to S retinal protein. In this work we study the relationship of specific IgG, IgA, and IgE auto-antibodies to Galectin (Gall) in sera of autoimmune uveitis (AIU) and infectious uveitis (IU). AIU and IU were previously defined by clinical findings. We measured specific IgG, IgA, IgE to Gal I by ELISA tests. Sixty five patients with uveitis were studied and compared with 30-matched healthy controls. Forty-nine cases had AIU and 16 had IU. We found specific IgG (+) to Gal-I in 12 of 49 AIU cases, specific IgA (+) to Gal-1 in 8 of 49 AIU cases and specific IgE (+) to Gal-1 in 10 of 49 cases of AIU. Overlapping specific IgG, IgA. IgE (+) to Gal-I was found in 6 of 49 cases of AIU, overlapping specific IgG and IgA (+) to Gal-I in 4 of 49 AIU cases; overlapping specific IgG and IgE (+) to Gal-1 in 5 of 49 AIU cases; overlapping specific IgA and IgE to Gal-1 in 3 of 49 AIU cases. One case of AIU was negative to specific IgG, IgA, IgE to Gal-l, as well as 13 IU and 28 of 30 controls. The toxoplasmic retinochoroiditis (n: 3) presented positive IgG and IgE to Gal-1 in 2 of 3 cases. To conclude, these results suggest the importance of specific IgG and IgE to Gal-1 in autoimmune uveitis as well as in toxoplasmic retinochoroiditis which revealed Th2 activation.
705
The Importance of Specific 'gG. 'gE Auto-Antibodies to Collagen II and the Relationship With Sensitivity to Alternuria in Antoimmune Inner Ear Diseases
Juan Carlos Muiho*, Carlos C~sar Castro§, Mar(a Jos~ Gregorio§, Marcela Ordo~ez§, Roger Carreras§, Marta Delia Romero-PiJfiguer§,
j ALLERGY CLIN IMMUNOL JANUARY 2002
701 AIncrease New Parameter of the Tumor Lysis Syndrome: Marked in Serum IgM M-Component in Two Patients With
,~a,~ Immune Reactivity to Human Recombinant Hsp-TO in Subjects qJl~JI Allergic to Mite
Waldenstr6m's Macroglobulinemia (WM) Treated With 2Chlorodeoxyadenosine(Cladribine)
Claudia Afferni, Bianca Barletta, Cinzia Butteroni, Patrizia lacovacci, Raffaella Tinghino, Gabriella Di Felice, Carlo Pini Institute Superiore di
Vandana M Krishna, Kurt J Bloch, Robert W Carey Massachusetts General Hospital, Boston, MA Tumor lysis syndrome (TLS) results from the rapid release of intracellular constituents into the circulation during tumor treatment. This release may result in hyperkalemia, hypercalcemia, hyperuricemia, and hyperphosphatemia. These abnormalities, in turn, may lead to life-threatening illness. TLS is associated with the treatment of leukemias, high-grade lymphomas, multiple myeloma and solid tumors. We observed two patients with WM who experienced a marked increase in their serum IgM M-component after treatment with 2-chlordeoxyadenosine (2-CDA). 2-CDA is a deoxyadenosine purine nucleoside analogue, which inhibits DNA synthesis and repair in actively dividing, as well as quiescent, cells. The major adverse effects of 2-CDA treatment axe myelosuppression and immunosuppression. TLS has been reported following treatment with 2-CDA. The bone marrow of one such patient showed necrosis of lymphoeytes. In our two patients, there was a marked increase in the concentration of the serum IgM soon after the first chemotherapy cycle was completed. The levels of serum IgM increased from 2580 mg/dL to 5900 mg/dL (relative viscosity 3.7) in the first patient and from 2360 mg/dL to 3600 mg/dL (relative viscosity 2.3) in the second patient. After the peak serum level of IgM was reached during the first treatment cycle, there was a steady decrease in concentration of IgM in both cases. Although neither of our patients experienced the hyperviscosity syndrome during treatment, the potential for this complication exists in patients with WM and higher levels of IgM before treatment. Release of large amounts of IgM M-component may constitute an additional element of TLS. Thus, patients with markedly elevated IgM concentration before treatment should be considered for plasmapheresis in anticipation of the rapid rise in IgM after chemotherapy.
Sanith, Rome, Italy The presence in nonatopic as well as allergic subjects of lgG antibodies specific for mite allergens is a well known evidence, but their physiological role in the allergic pathology is not completely understood. A recombinant allergen from Dermatophagoidesfarinae, named Mag 29, with a significant sequence homology to the caxboxyl-terminal region of the human cognate Hsp70, has been described, but is not known if patients' sera also react to human Hsp70. We detected IgG antibodies specific to recombinant human HSP-70, in sera from all the mite allergic tested, as well as from a group of nonatopic subjects, but we were not able to detect any specific IgE binding to this molecule. Moreover, we detected by ELISA and immunoblotting tecniques in the Dermatophagoidesfarinae extract a component of about 70 kDa, recognized by the IgG of the subjects tested and by a monoclonal antibody raised against Hsp-70 from bovine brain. The reactivity of this monoclonal antibody seemed to be highly cross-reactive, since it was able to bound a component of about 70 kDa in heterogeneous allergenic extracts, such as shrimp and peanut allergenic extracts, as well as in two human cellulax extracts, respectively one from peripheral blood lymphocytes and the other from a tumor epithelial cellular line. From these preliminary results, we may infer that IgG antibodies from allergic and nonatopic subjects specific for the human Hsp-70 could be cross-reactive with the component of about 70 kDa present in the crude extract of Dermatophagoidesfarinae, and also in several not-related allergenic extracts sharing antigenic epitopes with the human protein. The results of this study could be useful to understand the physiological role of the IgG antibodies specific to allergens, frequently detected both in allergic and in nonatopic subjects, in a peculiar case in which they recognize an allergenic epitope shared with self-determinants.
7 f~al'~ Abnormal Measles Serology and Autoimmunityin Autistic ChilIJIL- dren Vijendra K Singh, Courtney Nelson Utah State University, Logan, UT Immune factors such as autoimmunity may play a causal role in autism. We recently showed that many autistic children have autoantibodies to brain myelin basic protein (MBP) as well as elevated levels of measles virus antibodies. To extend this research further, we conducted a serological study of measles virus (MV), mumps virus (MuV), rubella virus (RV), cytomegalovirus (CMV), human herpesvirus-6 (HHV-6), measles-mumpsrubella (MMR), diptheria-pertussis-tetanus (DPT), diptheria-tetanus (DT) and hepatitis B (Hep B) and studied correlations with MBP autoantibodies. Antibodies were assayed in sera of autistic children (n=125) and normal children (n=92) by ELISA or immunoblotting methods. We found that autistic children have significantly (p=0.001) higher than normal levels of MV and MMR antibodies whereas the antibody levels of MuV, RV, CMV, HHV-6, DPT, DT or Hep B did not significantly differ between autistic and normal children. Immunoblotting analysis showed the presence of an unusual MMR antibody in 60% (75 of 125) of autistic children, but none of the 92 normal children had this antibody. Moreover, by using MMR blots and monoclonal antibodies, we found that the specific increase of MV antibodies or MMR antibodies was related to measles hemagglutinin antigen (MV-HA), but not to mumps or rubella viral proteins, of the MMR vaccine. In addition, over 90% of M M R antibody-positive autistic sera were also positive for MBP autoantibodies, suggesting a causal association between MMR and brain autoimmunity in autism. Stemming from this evidence, we suggest that an "atypical" measles infection in the absence of a rash but with neurological symptoms might be etiologically linked to autoimmunity in autism. (Supported by grants from the James Dougherty Jr Foundation, Unanue Foundation, Lettner Jr Foundation, Autism Autoimmunity Project and Autism Research Institute)
irma The Importance of Specific IgG. IgA and IcE to GaI-1 in Autoim~P'I' mune and Infectious Uveitis Marta Delia Romero-Piffiguer*, Juan Carlos Mui~o*, Mercedes Ferrero*, Claudio P Juarez§, Jos~ D Luna§, Gabriel Rabinovich¥ *Misericordia Hospital, C6rdoba, Argentina §Fundaci6n VER, C6rdoba, Argentina ¥Hospital Nacional de Clinicas Gral San Martin, Buenos Aires, Argentina In a previous work we described and characterized the presence of 16kDa galectin in chicken retina. The precise functions of the retinal galectin remain unknown. In previous studies we demonstrated specific IgG and IgE auto-antibodies to S retinal protein. In this work we study the relationship of specific IgG, IgA, and IgE auto-antibodies to Galectin (Gall) in sera of autoimmune uveitis (AIU) and infectious uveitis (IU). AIU and IU were previously defined by clinical findings. We measured specific IgG, IgA, IgE to Gal I by ELISA tests. Sixty five patients with uveitis were studied and compared with 30-matched healthy controls. Forty-nine cases had AIU and 16 had IU. We found specific IgG (+) to Gal-I in 12 of 49 AIU cases, specific IgA (+) to Gal-1 in 8 of 49 AIU cases and specific IgE (+) to Gal-1 in 10 of 49 cases of AIU. Overlapping specific IgG, IgA. IgE (+) to Gal-I was found in 6 of 49 cases of AIU, overlapping specific IgG and IgA (+) to Gal-I in 4 of 49 AIU cases; overlapping specific IgG and IgE (+) to Gal-1 in 5 of 49 AIU cases; overlapping specific IgA and IgE to Gal-1 in 3 of 49 AIU cases. One case of AIU was negative to specific IgG, IgA, IgE to Gal-l, as well as 13 IU and 28 of 30 controls. The toxoplasmic retinochoroiditis (n: 3) presented positive IgG and IgE to Gal-1 in 2 of 3 cases. To conclude, these results suggest the importance of specific IgG and IgE to Gal-1 in autoimmune uveitis as well as in toxoplasmic retinochoroiditis which revealed Th2 activation.
705
The Importance of Specific 'gG. 'gE Auto-Antibodies to Collagen II and the Relationship With Sensitivity to Alternuria in Antoimmune Inner Ear Diseases
Juan Carlos Muiho*, Carlos C~sar Castro§, Mar(a Jos~ Gregorio§, Marcela Ordo~ez§, Roger Carreras§, Marta Delia Romero-PiJfiguer§,