In Guillain-Barré syndrome (GBS), anti-ganglioside IgGantibodies (Abs) are considered important mediators ofdisease and in patients these are predominantly of thecomplement-fixing IgG1 and 3 subclasses. Previous studieshave demonstrated complement deposits on neural struc-tures in the peripheral nervous system early in the disease,whilst research conducted in rodent models also supportsa pathogenic role for complement-activating anti-gangliosideAbs. Recent research conducted in a small cohort of Italiandogs has indicated acute canine polyradiculoneuritis (ACP) torepresent a potential natural model for GBS; anti-gangliosideAbs were detected in 15/25 (60.0%) affected dogs, but in only1/34 (2.9%) control dogs (p < 0.01). To date, 162 canine serumsamples from ten institutions in four countries have beenexamined for Abs against 10 common glycolipids and theirheteromeric dimers, using the recently developed combina-torial microarray technique. In corroboration with our previousstudy, the predominant binding pattern observed was againstgangliosides GM2 and/or GA1 and their associated het-eromeric complexes. Overall, 49/73 (67.1%) ACP-sera con-tained such Abs, with 32 (43.8%) dogs exhibiting anti-GM2reactivity, 4 (5.5%) dogs exhibiting anti-GA1 reactivity and13 (17.8%) dogs exhibiting both. In comparison, only 3/40(7.5%) dogs with other cranial and peripheral neuropathies,myopathies and neuromuscular disorders and 5/49 (10.2%)non-neurological control dogs exhibited such Abs (p < 0.01).Further examination of nine anti-GM2/GA1 Ab-containingACP-sera revealed 8/9 sera to contain a high proportion ofIgG1 Abs, four of which also contained IgG3 Abs. Both thesesubclasses have been reported to be capable of fixing com-plement in dogs. In addition, activation of intermediate com-plement protein C3 by anti-GM2/GA1 Ab-containing sera wasdemonstrated on a solid phase assay. These results providefurther evidence that ACP is likely to represent a valuable nat-ural model of GBS.
COMPLEMENT-FIXING ANTI-GANGLIOSIDE ANTIBODIES IN ACUTE CANINE POLYRADICULONEURITIS / Rupp, A; Halstead, S; Day, M; Penderis, J; Bianchi, Ezio; Dondi, Maurizio; Volk, H; Bhakti, S; Pakozdy, A; Gandini, G; Gutierrez Quintana, R; Harcourt Brown, T; Smith, P; Ives, E; Rusbridge, C; Williston, Hj. - In: JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM. - ISSN 1085-9489. - 21:(2016), pp. 205-206. (Intervento presentato al convegno PNS/INC 2016 meeting tenutosi a Glasgow UK nel 21-24 giugno 2016).
COMPLEMENT-FIXING ANTI-GANGLIOSIDE ANTIBODIES IN ACUTE CANINE POLYRADICULONEURITIS
BIANCHI, Ezio;DONDI, Maurizio;
2016-01-01
Abstract
In Guillain-Barré syndrome (GBS), anti-ganglioside IgGantibodies (Abs) are considered important mediators ofdisease and in patients these are predominantly of thecomplement-fixing IgG1 and 3 subclasses. Previous studieshave demonstrated complement deposits on neural struc-tures in the peripheral nervous system early in the disease,whilst research conducted in rodent models also supportsa pathogenic role for complement-activating anti-gangliosideAbs. Recent research conducted in a small cohort of Italiandogs has indicated acute canine polyradiculoneuritis (ACP) torepresent a potential natural model for GBS; anti-gangliosideAbs were detected in 15/25 (60.0%) affected dogs, but in only1/34 (2.9%) control dogs (p < 0.01). To date, 162 canine serumsamples from ten institutions in four countries have beenexamined for Abs against 10 common glycolipids and theirheteromeric dimers, using the recently developed combina-torial microarray technique. In corroboration with our previousstudy, the predominant binding pattern observed was againstgangliosides GM2 and/or GA1 and their associated het-eromeric complexes. Overall, 49/73 (67.1%) ACP-sera con-tained such Abs, with 32 (43.8%) dogs exhibiting anti-GM2reactivity, 4 (5.5%) dogs exhibiting anti-GA1 reactivity and13 (17.8%) dogs exhibiting both. In comparison, only 3/40(7.5%) dogs with other cranial and peripheral neuropathies,myopathies and neuromuscular disorders and 5/49 (10.2%)non-neurological control dogs exhibited such Abs (p < 0.01).Further examination of nine anti-GM2/GA1 Ab-containingACP-sera revealed 8/9 sera to contain a high proportion ofIgG1 Abs, four of which also contained IgG3 Abs. Both thesesubclasses have been reported to be capable of fixing com-plement in dogs. In addition, activation of intermediate com-plement protein C3 by anti-GM2/GA1 Ab-containing sera wasdemonstrated on a solid phase assay. These results providefurther evidence that ACP is likely to represent a valuable nat-ural model of GBS.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.