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Autoimmune Dis. Published online Jul Aristo Vojdani 1 Immunosciences Lab. Joshua Berookhim 1 Immunosciences Lab. Author information Article notes Copyright and License information Disclaimer. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. This article has been cited by other articles in PMC. Abstract Multiple sclerosis MS is an autoimmune disease that affects the body's central nervous system.
Introduction Multiple sclerosis MS is characterized by the demyelination of a nerve's protective myelin sheaths in the brain and spinal cord, which occurs due to inflammation and attack by the body's own immune system [ 1 , 2 ]. Material and Methods 2. Determination of Specificity of Antibody Assay For the determination of the specificity of the AQP4 antibody reaction, serial dilutions of sera as well as inhibition studies were conducted using specific and nonspecific antigens.
Coefficients of Intra- and Interassay Variation Coefficients of intra-assay variation were calculated by running five samples eight times within a single assay.
Statistical Analysis We first calculated Pearson's correlation coefficient between each isotype lgG, lgA,. Results 3. Open in a separate window. Figure 1. Figure 2. Figure 3. Figure 4. Table 2 Results of the simple linear regression between each pair of lgG isotypes of the food proteins and brain proteins in RRMS patients.
Table 3 Results of the simple linear regression between each pair of lgA isotypes of the food proteins and brain proteins in RRMS patients. Table 4 Results of the simple linear regression between each pair of lgM isotypes of the food proteins and brain proteins in MS patients. Specificity of Antibodies In order to demonstrate specificity of detected antibody and to rule out nonspecific reaction, in addition to neural cell antigens and aquaporins, all sera were reacted with wells coated with HSA and OVA peptide —, followed by the addition of all reagents in the ELISA.
Figure 5. Figure 6. Figure 7. Figure 8.
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Figure 9. Figure Discussion In an earlier study [ 28 ], it was shown that several proteins in nature have a significant similarity in sequence and structure to human AQP4. Acknowledgment The authors would like to thank Joel Bautista for his work with some of the figures and in typing and editing the paper. Conflict of Interests The authors declare that there is no conflict of interests regarding the publication of this paper.
Authors' Contribution Aristo Vojdani designed the study, performed some of the experiments, and wrote the paper. References 1. Compston A. Multiple sclerosis. The Lancet. Nakahara J. Current concepts in multiple sclerosis: autoimmunity versus oligodendrogliopathy. Lublin F. Defining the clinical course of multiple sclerosis: results of an international survey. Defining the clinical course of multiple sclerosis: the revisions. Misaka T. A water channel closely related to rat brain aquaporin 4 is expressed in acid- and pepsinogen-secretory cells of human stomach. FEBS Letters.
Nagelhus E. Aquaporin-4 in the central nervous system: cellular and subcellular distribution and coexpression with KIR4. Nesic O. Acute and chronic changes in aquaporin 4 expression after spinal cord injury. Iacovetta C.
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The role of aquaporin 4 in the brain. Veterinary Clinical Pathology. Fallier-Becker P.
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Onset of aquaporin-4 expression in the developing mouse brain. International Journal of Developmental Neuroscience. Kim S. Clinical spectrum of CNS aquaporin-4 autoimmunity. Jarius S. Mechanisms of disease: aquaporin-4 antibodies in neuromyelitis optica. Nature Clinical Practice Neurology. Graber D. Neuromyelitis optica pathogenesis and aquaporin 4. Journal of Neuroinflammation. Lennon V. IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel.
The Journal of Experimental Medicine. AQP4 antibodies in neuromyelitis optica: diagnostic and pathogenetic relevance. Nature Reviews Neurology. Kim W. Characteristic brain magnetic resonance imaging abnormalities in central nervous system aquaporin-4 autoimmunity. Multiple Sclerosis. Petzold A. Neuromyelitis optica-IgG aquaporin-4 autoantibodies in immune mediated optic neuritis.
Dujmovic I. Temporal dynamics of cerebrospinal fluid anti-aquaporin-4 antibodies in patients with neuromyelitis optica spectrum disorders. Journal of Neuroimmunology. Weinshenker B. Neuromyelitis optica is distinct from multiple sclerosis. Archives of Neurology. Lalan S. Differentiation of neuromyelitis optica from multiple sclerosis on spinal magnetic resonance imaging.
International Journal of MS Care. Phuan P. Complement-dependent cytotoxicity in neuromyelitis optica requires aquaporin-4 protein assembly in orthogonal arrays. The Journal of Biological Chemistry. Lennon P. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Viswanathan S. The frequency of anti-aquaporin-4 Ig G antibody in neuromyelitis optica and its spectrum disorders at a single tertiary referral center in Malaysia. Multiple Sclerosis International. Takahashi T. Anti-aquaporin-4 antibody is involved in the pathogenesis of NMO: a study on antibody titre.
Bradl M. Anti-aquaporin-4 antibodies in neuromyelitis optica: how to prove their pathogenetic relevance? International MS Journal. Maurel C. Plant aquaporins: novel functions and regulation properties. Dean R. Purification and functional reconstitution of soybean nodulin An aquaporin with water and glycerol transport properties. Fleurat-Lessard P. Annals of Botany. Vaishnav R. Aquaporin 4 molecular mimicry and implications for neuromyelitis optica. Egg R. Berger T. Antimyelin antibodies as a predictor of clinically definite multiple sclerosis after a first demyelinating event.
Essays, memories, and even a little history…
The New England Journal of Medicine. Vojdani A. Journal of Internal Medicine.
Reindl M. Antibodies against the myelin oligodendrocyte glycoprotein and the myelin basic protein in multiple sclerosis and other neurological diseases: a comparative study. Isoardo G. Anti-GM1 and anti-sulfatide antibodies in polyneuropathies: threshold titers and accuracy. Acta Neurologica Scandinavica. Connolly A. Choi H. SB as a serum marker for early detection of brain metastasis in lung cancer. Marchi N. By the time of the Napoleonic Wars, no-one could doubt their Englishness. On July 26th, a mass meeting of Londoners unanimously declared its 'determination to stand or fall with our King and country' because:.
The independence and existence of the British Empire The declaration was signed by the chairman: Jacob Bosanquet, grandson of David Bosanquet who had taken refuge from Languedoc in Assimilation was not accomplished without strains within Huguenot families. Some of the steps that might be involved are revealed in the autobiography of Sir Samuel Romilly , a law reformer whose career was important for its long and successful. His great-grandfather, a landowner at Montpellier, had remained in the south of France after the Revocation, but continued to worship in Protestant ways within the security of his own home, and brought up his children as Protestants.
It was Samuel's grandfather, Etienne, who became a refugee in , at the age of seventeen. He went to Geneva for the specific purpose of receiving Communion, and there decided not to return home but to go instead to London. Only then did he inform his family of his decision, but his father accepted the situation and sent money to him from France which helped him establish himself as a wax-'bleacher in Hoxton, It is typical of first-generation refugees to marry others of their own kind, and Etienne married Judith de Monsallier, the daughter of another Huguenot immigrant.
Samuel Romilly's father, Peter, was apprenticed to a Frenchman in the City, a jeweller named Lafosse. In due course Peter too married the daughter of a refugee, Margaret Gamault, so Samuel was brought up in surroundings which retained strong Huguenot influences. He described his father as attaching more importance to practical charitable behaviour towards his fellow men than to forms of worship, but Peter made his family regularly attend morning and evening worship on Sundays, alternating between the parish church and the French chapel in which he had a pew.
Otherwise he was far from impressed:. Nothing was ever worse calculated to inspire the mind of a child with respect for. Most of the descendants of the refugees were born and bred in England, and desired nothing less than to preserve the memory of their origin; and their chapels were therefore ill-attended. A large uncouth room, the avenues to which were narrow courts and dirty alleys, and which, when you entered it, presented to the view only irregular unpainted pews and dusty plastered walls; a congregation consisting principally of some strange-looking old women scattered here and there, one or two in a pew, and a clergyman reading the service and preaching in a monotonous tone of voice, and in a language not familiar to me, was not likely either to impress my mind with much religious awe, or to attract my attention to the doctrines which were delivered.
Nor did he respect the school to which he was sent, 'of which the sole recommendation seems to have been that it had once been kept by a French refugee, and that the sons of many refugees were still scholars at it'. Writing, arithmetic, and the rules of French grammar. As for 'the more familiar use' of French, that was something which he and his brother acquired at home, for it remained 'a rule established by my father, that French should be spoken in the family on a Sunday morning, the only time Despite his strictures on the French services he had known in his youth, Samuel Romilly continued to attend the chapel, and found it a changed place when a new minister, John Roget, replaced the old man whose monotony had so bored him.
Roget indeed became a close friend, and married his sister Catherine. Samuel's Huguenot background must have continued to influence him, and in he followed his elder brother and father in being elected a director of the French Protestant Hospital. But by and large it was the members of his — the third — generation of refugees who were the last to show any profound awareness of the Huguenot character of their families. In those Protestants who remained in France finally won toleration, and shortly afterwards special rights were offered to Huguenot descendants who might wish to return there.
Very few of those who had crossed the Channel can have been tempted, for assimilation was complete. What had been French had become British. Various stages can be discerned in the process of assimilation. Just as modern West Indian immigrants may be specifically Grenadian or Trinidadian in the first generation but more generally West Indian in the second, so the Huguenots moved from a close attachment to their provinces of origin towards simply a consciousness of having had roots in France.
Between the s and , a series of Friendly Societies — the first in England — were founded, almost all with a French regional basis: the 'Societe des Enfants de Nimes', the Society of Dauphine, the Norman Friendly Society and so on. In London, where there were many French congregations, certain churches drew markedly on some provinces rather than others, so that in Spitalfields refugees from Picardy were likely to attend the church of St Jean, while those from Poitou were drawn to La Patente.
Refuge relief — a massive operation which involved the transfer of over one and. La Providence , the French Protestant Hospital, was founded in , also in London; it still exists today, located now at Rochester in the form of flatlets for the elderly. French congregations dwindled in number and lost their regional bases of membership. The Westminster French Protestant School, founded in for descendants of the refugees, survived into this century and continues to assist with their education in the new guise of the Westminster French Protestant School Foundation.
Calvinism, with its elders to supervise moral behaviour and its deacons to administer poor relief, was always a practical form of religion. Its founder, John Calvin, wanted people to worship God as was their duty, and established an organisation designed to achieve that end. The Friendly Societies with their mutual aid schemes, the Maisons de Charite, the French Protestant Hospital and School, all have their roots in the religious commitment that had prompted the Huguenots to seek refuge in the first place.
For this was one wave of refugees whose destitution was due almost wholly to their adherence to their beliefs. The Protestants who reached Tudor England included a substantial proportion — nearly half, perhaps — whose motivation was primarily economic; and they came from lands divided by civil war, and to that extent could be charged by their enemies with sedition.
With the exception of the Camisard rebellion in the Cevennes, they made no effort to resist the state authorities except through flight itself. Since the French government had no wish to lose such useful citizens, that was a dangerous option. Soldiers were patrolling the land frontiers, ships the sea coasts.
Capture meant fines and imprisonment at the least, and possibly transportation to the New World, death or — a still worse fate — a lifetime's service chained aboard the French king's galleys. Historians sometimes write as though religion was no longer the same motivating force in the late seventeenth century that it had been earlier, at the time of the Reformation and Counter-Reformation. The story of the Huguenots, or indeed the way in which James II threw away his throne in his vain and unpopular efforts to secure greater toleration and equal opportunities for his fellow Catholics in England, suggests that this view needs reconsideration.
From the secular viewpoint of the twentieth century, it is surprising that Louis XIV's advisers should have been willing to countenance the loss of so many useful, peaceful and productive subjects, and astonishing that perhaps a quarter of the Protestants in France at the time were prepared to accept the loss of land and possessions and embrace the dangers inherent in the option of flight. If their willingness to work hard, to persevere and to lead frugal, upright lives can be ascribed to their religious motivation, the remarkable versatility shown by some of the Huguenots seems rather the product of their displacement and situation as refugees.
John Dollond was a silkweaver in Spitalfields when he developed an interest in optics, set his son up as an optician and then abandoned his earlier craft and joined him; he became a Fellow of the Royal Society and won a Copley gold medal, and the firm he founded has grown into that of Dollond and Aitchison. James Vauloue, who invented the machine that drove in the piles for the first Westminster Bridge, was a watchmaker.
The career of Jacques Fontaine, who was training for the ministry when he escaped from France to Appledore near. Barnstaple, Devon in , is fascinating. He had no business or craft training, but was determined to make his own way and not rely on charity. Moving to Taunton in neighbouring Somerset, he opened a shop and began to make cloth.
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So successful was he that by he had made a thousand pounds, but he had also aroused local jealousy — and he still aimed to minister to a larger French congregation than Taunton could provide. Packing up, he moved to Cork in Ireland, where, in addition to his ministry, he engaged his formidable energies first in broadcloth manufacture, then in a fishing business.
When he died in the early s, he was running a school in Dublin, while most of his children had gone to Virginia to make yet another new start. Fontaine was a forceful man, not noted for compromise or. The Huguenots as a whole shared his quality of determination, yet they contributed to a European-wide movement towards greater toleration and understanding during the eighteenth century.
This was partly because their own example underlined the unreasonableness and folly of displacing so many useful citizens in the search for religious uniformity. Further, when they voted with their feet to disobey their government and flee, they raised fundamental questions about the rights of the subject and of the individual conscience.
The Huguenots had to answer those questions to their own satisfaction, and to defend their actions to their fellow countrymen still in France. Moreover, by their dispersion they helped create a more international community in Europe than had existed since pre-Reformation days. Pierre Bayle, a refugee in the Netherlands, exercised an important influence through his personal advocacy of toleration and freedom of conscience and through his sceptical and scientific method which pointed the way to Voltaire and other thinkers of the Enlightenment.
Other Huguenots influenced a new cross-fertilisation of English and continental ideas. As the refugees rooted themselves in Britain, they began to explore the variety of religious experience around them. In the first generation after the Revocation, the majority clung to the form of worship they had known in France, while a minority used the Anglican Prayer Book translated into French.
As their descendants became English, they came to play a part not only in Presbyterianism which was closest to the French Calvinist forms and Anglicanism, but in early Methodism — Vincent Perronet was the Wesleys' right-hand man — and most other branches of Protestantism. And in the nineteenth century, that most notable of English Catholics, Cardinal Newman, was the son of a Fourdrinier mother.
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