Jacquetta of Luxembourg
by Michael Long
Jacquetta of Luxembourg was the eldest child of the French Count of St Pol; her family descended from Charlemagne and were cousins to the Holy Roman Emperor. She grew up with war between France and England raging around her.
John, Duke of Bedford was the youngest son of King Henry IV. Having lost his wife to plague in 1432, he arranged to marry the seventeen-year-old Jacquetta, who was his social equal by her birth. Although married for two years they were childless when John died in September 1435. The King instructed Jacquetta to come to England and ordered Sir Richard Woodville, to arrange it.
However, Jacquetta and Richard fell in love, but Richard was a poor knight, far below Jacquetta in social status. Nonetheless, they married secretly thus thwarting any plans King Henry may have had to marry her off to a wealthy English lord. Theirs was a morganatic marriage, where one of the partners, most often the wife, was socially inferior. Henry was enraged and fined the couple £1000. He did however allow their heirs to inherit, which was unusual for morganatic marriages in England.
Illuminated miniature depicting the marriage of Edward IV and Elizabeth Woodville, ‘Anciennes Chroniques d’Angleterre’ by Jean de Wavrin, 15th century
Being the widow of Henry V’s brother and aunt to the King, royal protocol gave Jacquetta the highest rank at court of any female except Henry’s wife, Margaret of Anjou, to whom Jacquetta was related by marriage. She even ‘outranked’ the King’s mother and was referred to as the ‘Duchess of Bedford,’ retaining the title from her first marriage. Richard and Jacquetta lived in their manor house at Grafton Regis near Northampton producing fourteen children, the eldest, Elizabeth being born in 1437.
In 1448 Richard was created Lord Rivers: his advancement ensured his family supported Henry VI in the dynastic feuding of the Wars of the Roses. The situation changed with the Yorkist victory at the Battle of Towton in 1461 and the seizure of the throne by Edward IV. By the spring of 1464, Jacquetta’s daughter Elizabeth was a widow, her Lancastrian husband having been killed in 1461. Within a few months, Elizabeth was married to the young King Edward IV.
Contemporaries were shocked that the King would marry a Lancastrian widow and a ‘commoner’ at that, for Jacquetta’s rank did not pass to her children. The King was expected to marry a foreign princess for diplomatic advantages, not for love. The English nobility was also alarmed, as the twelve unmarried siblings of the new Queen would require suitable ‘noble’ marriages. Little wonder that the Woodville family were considered ‘upstarts’ at court.
Richard Neville, Earl of Warwick who had been instrumental in Edward gaining the throne, stood to lose the most. His influence waned as the Woodvilles became more influential at court. In 1469, he launched a coup against Edward imprisoning him in Middleham Castle and ruling in his name. Warwick captured Rivers and his younger brother and had both executed. Warwick then had one of his close supporters accuse Jacquetta of using witchcraft in order to force Edward into marrying her daughter Elizabeth (below).
The mother of the Queen of England was put on trial for maleficium (using sorcery). The prosecution produced small lead figures as evidence that Jacquetta had used them to cast her ‘marriage’ spell.
Unsurprisingly, Jacquetta was convicted but meanwhile King Edward was released and reclaimed his crown, forcing Warwick into exile. In February 1470 Jacquetta was cleared of all charges
The power struggle between Edward and Warwick continued and in September 1470, Edward was forced to flee to the Netherlands. Jacquetta and the heavily pregnant Queen Elizabeth sought sanctuary in Westminster Abbey. In November she gave birth to the future King Edward V, attended by her mother, her doctor and a local butcher.
When Edward returned to England at the head of an army in April 1471, he entered London in triumph and Jacquetta and Elizabeth could leave sanctuary. His victories at Barnet and Tewkesbury that year guaranteed the Yorkist kingship in England.
Jacquetta died the following year aged 56 and was buried at Grafton, though no record of her tomb survives. Recently, one legacy has come to light. Research by gene specialists indicates that Jacquetta was a carrier of the rare Kell-Antigen-Mcleod syndrome causing impaired fertility and psychotic behavioural changes in the male descendants of the family.
Edward IV had ten children with Elizabeth Woodville and more children with other women, seven of whom survived him. Thus it is unlikely that the K-antigen was present in his parents. Edward’s father, Richard Duke of York had 13 children. Clearly, the Yorkist line was very fertile. Similarly, Richard Woodville had 14 children with Jacquetta, suggesting that he was unlikely to be the source of the K-antigen.
However, if Jacquetta were the source, her daughters would have carried it and fertility problems could have been apparent in half of Edward IV’s male children and in half of male grandchildren. Unfortunately, none of Edward’s IV sons reached manhood. One died in infancy and the remaining two were the ‘Princes in the Tower’.
The wives of Jacquetta’s great-grandson, Henry VIII (above) suffered numerous miscarriages which may be explained if Henry’s blood carried the Kell-Antigen. A woman who is Kell-Antigen negative and a Kell-Antigen positive male will produce a healthy, Kell-Antigen positive child in a first pregnancy. However, the antibodies she produces will cross the placenta and attack the fetus in subsequent pregnancies. When one considers the history of both Catherine of Aragon and Anne Boleyn, both of whom produced healthy first-borns followed by multiple miscarriages, this becomes a compelling theory.
If Jacquetta also carried the Mcleod-Syndrome, unique to the Kell disorder, it also explains her great-grandson Henry VIII’s physical and personality changes in the 1530s; weight gain, paranoia and personality change are characteristic of Kell-Antigen/Mcleod -Syndrome. That Jacquetta’s male descendants were reproductive ‘failures’ while her female line was reproductively successful does suggest that her legacy was to pass the Kell antigen to the Tudor line, ultimately causing its demise.
https://www.verywellfamily.com/can-being-rh-negative-cause-a-miscarriage-2371474
Kell antigen system
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Kell protein | |
---|---|
Identifiers | |
Symbol | KEL |
Alt. symbols | ECE3, CD238 |
NCBI gene | 3792 |
HGNC | 6308 |
OMIM | 110900 |
RefSeq | NM_000420 |
UniProt | P23276 |
Other data | |
Locus | Chr. 7 q33 |
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The Kell antigen system (also known as Kell–Cellano system) is a human blood group system, that is, group of antigens on the human red blood cell surface which are important determinants of blood type and are targets for autoimmune or alloimmune diseases which destroy red blood cells. The Kell antigens are K, k, Kpa, Kpb, Jsa and Jsb.[1] The Kell antigens are peptides found within the Kell protein, a 93-kilodalton transmembrane zinc-dependent endopeptidase which is responsible for cleaving endothelin-3.[2][3]
Contents
Protein[edit]
The KEL gene encodes a type II transmembrane glycoprotein[4] that is the highly polymorphic Kell blood group antigen. The Kell glycoprotein links via a single disulfide bond to the XK membrane protein[5] that carries the Kx antigen. The encoded protein contains sequence and structural similarity to members of the neprilysin (M13) family of zinc endopeptidases.[6]
There are several alleles of the gene which creates Kell protein. Two such alleles, K1 (Kell) and K2 (Cellano), are the most common. The kell protein is tightly bound to a second protein, XK, by a disulfide bond. Absence of the XK protein (such as through genetic deletion or through a single point mutation within the coding region of the XK gene[7]), leads to marked reduction of the Kell antigens on the red blood cell surface. Absence of the Kell protein (K0), however, does not affect the XK protein.[8]
The Kell protein has also recently been designated CD238 (cluster of differentiation 238).
Disease association[edit]
Interpretation of antibody panel to detect patient antibodies towards the most relevant human blood group systems, including Kell.Further information: Blood compatibility testing
Kell antigens are important in transfusion medicine, autoimmune hemolytic anemia and hemolytic disease of the newborn (anti-Kell). Anti-K is the next most common immune red cell antibody after those in the ABO and Rh system. Anti-K typically presents as IgG class alloantibody. Individuals lacking a specific Kell antigen may develop antibodies against Kell antigens when transfused with blood containing that antigen. This is particularly true for the “K” antigen which shows a relatively high antigenicity and moderately low frequency (~9%) in Caucasian populations. Anti-K can also occur following transplacental hemorrhage (TPH) associated with childbirth making Kell an important concern for hemolytic disease of the newborn. Following the formation of anti-K, subsequent blood transfusions may be marked by destruction of the new cells by these antibodies, a process known as hemolysis. Anti-K does not bind complement, therefore hemolysis is extravascular. Individuals without K antigens(K0) who have formed an antibody to a K antigen, must be transfused with blood from donors who are also K0 to prevent hemolysis.
Autoimmune hemolytic anemia (AIHA) occurs when the body produces an antibody against a blood group antigen on its own red blood cells. The antibodies lead to destruction of the red blood cells with resulting anemia. Similarly, a pregnant woman may develop antibodies against fetal red blood cells, resulting in destruction, anemia, and hydrops fetalis in a process known as hemolytic disease of the newborn (HDN). Both AIHA and HDN may be severe when caused by anti-Kell antibodies,[9] as they are the most immunogenic antigens after those of the ABO and Rhesus blood group systems.
McLeod phenotype[edit]
Main article: McLeod syndrome
McLeod phenotype (or McLeod syndrome) is an X-linked anomaly of the Kell blood group system in which Kell antigens are poorly detected by laboratory tests. The McLeod gene encodes the XK protein, a protein with structural characteristics of a membrane transport protein but of unknown function. The XK appears to be required for proper synthesis or presentation of the Kell antigens on the red blood cell surface.
History[edit]
The Kell group was named after the first patient described with antibodies to K1, a pregnant woman named Mrs. Kellacher in 1945.[10] Mrs. Cellano was likewise a pregnant woman with the first described antibodies to K2. The K0 phenotype was first described in 1957 and the McLeod phenotype was found in Hugh McLeod, a Harvard dental student, in 1961.[11][12] King Henry VIII of England may have had Kell-positive blood type, explaining the deaths of seven of his ten children at, or soon after, birth, and suggesting that his mental deterioration around age 40 could be explained by McLeod Syndrome;[13] this was supported by the revelation that Henry may have inherited Kell from his maternal great-grandmother, Jacquetta of Luxembourg.[14]
Other associations[edit]
Evidence supports a genetic link between the Kell blood group (on chromosome 7 q33) and the ability to taste phenylthiocarbamide, or PTC, a bitter-tasting thiourea compound.[15][16] Bitter taste receptor proteins in the taste buds of the tongue that recognise PTC are encoded on nearby chromosome locus 7 q35-6.
References[edit]
- ^ Smart, E.; Armstrong, B. (2008). “Blood group systems”. ISBT Science Series. 3 (2): 68–92. doi:10.1111/j.1751-2824.2008.00188.x. ISSN 1751-2816.
- ^ Lee S, Wu X, Reid M, Zelinski T, Redman C (February 1995). “Molecular basis of the Kell (K1) phenotype”. Blood. 85 (4): 912–6. doi:10.1182/blood.V85.4.912.bloodjournal854912. PMID 7849312.
- ^ Lee S, Lin M, Mele A, Cao Y, Farmar J, Russo D, Redman C (August 1999). “Proteolytic processing of big endothelin-3 by the kell blood group protein”. Blood. 94 (4): 1440–50. doi:10.1182/blood.V94.4.1440. PMID 10438732. Archived from the original on 2013-04-14.
- ^ Russo DC, Lee S, Reid M, Redman CM. Topology of Kell blood group protein and the expression of multiple antigens by transfected cells. Blood. 1994 Nov 15;84(10):3518-23.
- ^ Russo DC, Redman C, Lee S. Association of XK and Kell blood group proteins. J Biol Chem. 1998 May 29;273(22):13950-6.
- ^ “Entrez Gene: KEL”.
- ^ Russo DC, Lee S, Reid ME, Redman CM (Mar 2002). “Point mutations causing the McLeod phenotype”. Transfusion. 42 (3): 287–93. doi:10.1046/j.1537-2995.2002.00049.x. PMID 11961232. S2CID 41663851.
- ^ Yu LC, Twu YC, Chang CY, Lin M (March 2001). “Molecular basis of the Kell-null phenotype: a mutation at the splice site of human KEL gene abolishes the expression of Kell blood group antigens”. The Journal of Biological Chemistry. 276 (13): 10247–52. doi:10.1074/jbc.M009879200. PMID 11134029.
- ^ Weiner CP, Widness JA (February 1996). “Decreased fetal erythropoiesis and hemolysis in Kell hemolytic anemia”. American Journal of Obstetrics and Gynecology. 174 (2): 547–51. doi:10.1016/S0002-9378(96)70425-8. PMID 8623782.
- ^ Coombs RRA, Mourant AE, Race RR. A new test for the detection of weak and incomplete Rh agglutinins. Br J Exp Pathol 1945;26:255
- ^ Chown B, Lewis M, Kaita K (October 1957). “A new Kell blood-group phenotype”. Nature. 180 (4588): 711. Bibcode:1957Natur.180..711C. doi:10.1038/180711a0. PMID 13477267. S2CID 4187507.
- ^ Allen FH, Krabbe SM, Corcoran PA (September 1961). “A new phenotype (McLeod) in the Kell blood-group system”. Vox Sanguinis. 6 (5): 555–60. doi:10.1111/j.1423-0410.1961.tb03203.x. PMID 13860532. S2CID 30275809.
- ^ Whitley CB, Kramer K (December 2010). “A new explanation for the reproductive woes and midlife decline of Henry VIII”. The Historical Journal. 53 (4): 827–848. doi:10.1017/S0018246X10000452.
- ^ Stride P, Lopes Floro K (2013). “Henry VIII, McLeod syndrome and Jacquetta’s curse”. The Journal of the Royal College of Physicians of Edinburgh. 43 (4): 353–60. doi:10.4997/JRCPE.2013.417. PMID 24350322.
- ^ Crandall BF, Spence MA (1974). “Linkage relations of the phenylthiocarbamide locus (PTC)”. Human Heredity. 24 (3): 247–52. doi:10.1159/000152657. PMID 4435792.
- ^ Conneally PM, Dumont-Driscoll M, Huntzinger RS, Nance WE, Jackson CE (1976). “Linkage relations of the loci for Kell and phenylthiocarbamide taste sensitivity”. Human Heredity. 26 (4): 267–71. doi:10.1159/000152813. PMID 976995.
External links[edit]
- Online Mendelian Inheritance in Man (OMIM): 110900 – OMIM entry for Kell protein
- Online Mendelian Inheritance in Man (OMIM): 314850 – OMIM entry for XK protein
- Kell at BGMUT Blood Group Antigen Gene Mutation Database at NCBI, NIH
- KEL+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)