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1. Genome-wide association study identifies Sjögrens risk loci with functional implications in immune and glandular cells.

Author

Khatri, Bhuwan, Tessneer, Kandice, Rasmussen, Astrid, Aghakhanian, Farhang, Reksten, Tove, Adler, Adam, Alevizos, Ilias, Anaya, Juan-Manuel, Aqrawi, Lara, Baecklund, Eva, Brun, Johan, Bucher, Sara, Eloranta, Maija-Leena, Engelke, Fiona, Forsblad-dElia, Helena, Glenn, Stuart, Hammenfors, Daniel, Imgenberg-Kreuz, Juliana, Jensen, Janicke, Johnsen, Svein, Jonsson, Malin, Kvarnström, Marika, Kelly, Jennifer, Li, He, Mandl, Thomas, Martín, Javier, Nocturne, Gaétane, Norheim, Katrine, Palm, Øyvind, Skarstein, Kathrine, Stolarczyk, Anna, Taylor, Kimberly, Teruel, Maria, Theander, Elke, Venuturupalli, Swamy, Wallace, Daniel, Grundahl, Kiely, Hefner, Kimberly, Radfar, Lida, Lewis, David, Stone, Donald, Kaufman, C, Brennan, Michael, Guthridge, Joel, James, Judith, Scofield, R, Gaffney, Patrick, Criswell, Lindsey, Jonsson, Roland, Eriksson, Per, Bowman, Simon, Omdal, Roald, Rönnblom, Lars, Warner, Blake, Rischmueller, Maureen, Witte, Torsten, Farris, A, Mariette, Xavier, Alarcon-Riquelme, Marta, Shiboski, Caroline, Wahren-Herlenius, Marie, Ng, Wan-Fai, Sivils, Kathy, Adrianto, Indra, Nordmark, Gunnel, and Lessard, Christopher

Subjects
Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Sjogrens Syndrome
Abstract

Sjögrens disease is a complex autoimmune disease with twelve established susceptibility loci. This genome-wide association study (GWAS) identifies ten novel genome-wide significant (GWS) regions in Sjögrens cases of European ancestry: CD247, NAB1, PTTG1-MIR146A, PRDM1-ATG5, TNFAIP3, XKR6, MAPT-CRHR1, RPTOR-CHMP6-BAIAP6, TYK2, SYNGR1. Polygenic risk scores yield predictability (AUROC = 0.71) and relative risk of 12.08. Interrogation of bioinformatics databases refine the associations, define local regulatory networks of GWS SNPs from the 95% credible set, and expand the implicated gene list to >40. Many GWS SNPs are eQTLs for genes within topologically associated domains in immune cells and/or eQTLs in the main target tissue, salivary glands.

Published
2022

2. Author Correction: Genome-wide association study identifies Sjögren’s risk loci with functional implications in immune and glandular cells

Author

Khatri, Bhuwan, Tessneer, Kandice L., Rasmussen, Astrid, Aghakhanian, Farhang, Reksten, Tove Ragna, Adler, Adam, Alevizos, Ilias, Anaya, Juan-Manuel, Aqrawi, Lara A., Baecklund, Eva, Brun, Johan G., Bucher, Sara Magnusson, Eloranta, Maija-Leena, Engelke, Fiona, Forsblad-d’Elia, Helena, Glenn, Stuart B., Hammenfors, Daniel, Imgenberg-Kreuz, Juliana, Jensen, Janicke Liaaen, Johnsen, Svein Joar Auglænd, Jonsson, Malin V., Kvarnström, Marika, Kelly, Jennifer A., Li, He, Mandl, Thomas, Martín, Javier, Nocturne, Gaétane, Norheim, Katrine Brække, Palm, Øyvind, Skarstein, Kathrine, Stolarczyk, Anna M., Taylor, Kimberly E., Teruel, Maria, Theander, Elke, Venuturupalli, Swamy, Wallace, Daniel J., Grundahl, Kiely M., Hefner, Kimberly S., Radfar, Lida, Lewis, David M., Stone, Donald U., Kaufman, C. Erick, Brennan, Michael T., Guthridge, Joel M., James, Judith A., Scofield, R. Hal, Gaffney, Patrick M., Criswell, Lindsey A., Jonsson, Roland, Eriksson, Per, Bowman, Simon J., Omdal, Roald, Rönnblom, Lars, Warner, Blake, Rischmueller, Maureen, Witte, Torsten, Farris, A. Darise, Mariette, Xavier, Alarcon-Riquelme, Marta E., Shiboski, Caroline H., Wahren-Herlenius, Marie, Ng, Wan-Fai, Sivils, Kathy L., Adrianto, Indra, Nordmark, Gunnel, and Lessard, Christopher J.

Published
2023
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3. Author Correction: Genome-wide association study identifies Sjögren’s risk loci with functional implications in immune and glandular cells

Author

Khatri, Bhuwan, Tessneer, Kandice L., Rasmussen, Astrid, Aghakhanian, Farhang, Reksten, Tove Ragna, Adler, Adam, Alevizos, Ilias, Anaya, Juan-Manuel, Aqrawi, Lara A., Baecklund, Eva, Brun, Johan G., Bucher, Sara Magnusson, Eloranta, Maija-Leena, Engelke, Fiona, Forsblad-d’Elia, Helena, Glenn, Stuart B., Hammenfors, Daniel, Imgenberg-Kreuz, Juliana, Jensen, Janicke Liaaen, Johnsen, Svein Joar Auglænd, Jonsson, Malin V., Kvarnström, Marika, Kelly, Jennifer A., Li, He, Mandl, Thomas, Martín, Javier, Nocturne, Gaétane, Norheim, Katrine Brække, Palm, Øyvind, Skarstein, Kathrine, Stolarczyk, Anna M., Taylor, Kimberly E., Teruel, Maria, Theander, Elke, Venuturupalli, Swamy, Wallace, Daniel J., Grundahl, Kiely M., Hefner, Kimberly S., Radfar, Lida, Lewis, David M., Stone, Donald U., Kaufman, C. Erick, Brennan, Michael T., Guthridge, Joel M., James, Judith A., Scofield, R. Hal, Gaffney, Patrick M., Criswell, Lindsey A., Jonsson, Roland, Eriksson, Per, Bowman, Simon J., Omdal, Roald, Rönnblom, Lars, Warner, Blake, Rischmueller, Maureen, Witte, Torsten, Farris, A. Darise, Mariette, Xavier, Alarcon-Riquelme, Marta E., Shiboski, Caroline H., Wahren-Herlenius, Marie, Ng, Wan-Fai, Sivils, Kathy L., Adrianto, Indra, Nordmark, Gunnel, and Lessard, Christopher J.

Published
2022
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4. Variants in the DDX6-CXCR5 autoimmune disease risk locus influence the regulatory network in immune cells and salivary gland

Author

Wiley, Mandi M, primary, Khatri, Bhuwan, additional, Joachims, Michelle L, additional, Tessneer, Kandice L, additional, Stolarczyk, Anna M, additional, Rasmussen, Astrid, additional, Anaya, Juan-Manuel, additional, Aqrawi, Lara A, additional, Bae, Sang-Cheol, additional, Baecklund, Eva, additional, Bjork, Albin, additional, Brun, Johan G, additional, Bucher, Sara Magnusson, additional, Dand, Nick, additional, Eloranta, Maija-Leena, additional, Engelke, Fiona, additional, Forsblad-d'Elia, Helena, additional, Fugmann, Cecilia, additional, Glenn, Stuart B, additional, Gong, Chen, additional, Gottenberg, Jacques-Eric, additional, Hammenfors, Daniel, additional, Imgenberg-Kreuz, Juliana, additional, Jensen, Janicke Liaaen, additional, Johnsen, Svein Joar Auglaend, additional, Jonsson, Malin V, additional, Kelly, Jennifer A, additional, Khanam, Sharmily, additional, Kim, Kwangwoo, additional, Kvarnstrom, Marika, additional, Mandl, Thomas, additional, Martin, Javier, additional, Morris, David L, additional, Nocturne, Gaetane, additional, Norheim, Katrine Braekke, additional, Olsson, Peter, additional, Palm, Oyvind, additional, Pers, Jacques-Olivier, additional, Rhodus, Nelson L, additional, Sjowall, Christopher, additional, Skarstein, Kathrine, additional, Taylor, Kimberly E, additional, Tombleson, Phil, additional, Thorlacius, Gudny Ella, additional, Venuturupalli, Swamy, additional, Vital, Edward M, additional, Wallace, Daniel J., additional, Grundahl, Kiely M, additional, Radfar, Lida, additional, Brennan, Michael T, additional, James, Judith A, additional, Scofield, R. Hal, additional, Gaffney, Patrick M, additional, Criswell, Lindsey A, additional, Jonsson, Roland, additional, Appel, Silke, additional, Eriksson, Per, additional, Bowman, Simon J, additional, Omdal, Roald, additional, Ronnblom, Lars, additional, Warner, Blake M., additional, Rischmueller, Maureen, additional, Witte, Torsten, additional, Farris, A. Darise, additional, Mariette, Xavier, additional, Shiboski, Caroline H, additional, Wahren-Herlenius, Marie, additional, Alarcon-Riquelme, Marta E, additional, Ng, Wan-Fai, additional, Sivils, Kathy L., additional, Guthridge, Joel M, additional, Adrianto, Indra, additional, Vyse, Timothy J, additional, Tsao, Betty P, additional, Nordmark, Gunnel, additional, and Lessard, Christopher J, additional

Published
2023
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5. Klinefelter's syndrome (47,XXY) is in excess among men with Sjögren's syndrome

Author

Harris, Valerie M., Sharma, Rohan, Cavett, Joshua, Kurien, Biji T., Liu, Ke, Koelsch, Kristi A., Rasmussen, Astrid, Radfar, Lida, Lewis, David, Stone, Donald U., Kaufman, C. Erick, Li, Shibo, Segal, Barbara, Wallace, Daniel J., Weisman, Michael H., Venuturupalli, Swamy, Kelly, Jennifer A., Alarcon-Riquelme, Marta E., Pons-Estel, Bernardo, Jonsson, Roland, Lu, Xianglan, Gottenberg, Jacques-Eric, Anaya, Juan-Manuel, Cunninghame-Graham, Deborah S., Huang, Andrew J.W., Brennan, Michael T., Hughes, Pamela, Alevizos, Ilias, Miceli-Richard, Corinne, Keystone, Edward C., Bykerk, Vivian P., Hirschfield, Gideon, Xie, Gang, Ng, Wan-Fai, Nordmark, Gunnel, Bucher, Sara Magnusson, Eriksson, Per, Omdal, Roald, Rhodus, Nelson L., Rischmueller, Maureen, Rohrer, Michael, Wahren-Herlenius, Marie, Witte, Torsten, Mariette, Xavier, Lessard, Christopher J., Harley, John B., Sivils, Kathy L., and Scofield, R. Hal

Published
2016
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6. Brief Report: Rare X Chromosome Abnormalities in Systemic Lupus Erythematosus and Sjögrenʼs Syndrome

Author

Sharma, Rohan, Harris, Valerie M., Cavett, Joshua, Kurien, Biji T., Liu, Ke, Koelsch, Kristi A., Fayaaz, Anum, Chaudhari, Kaustubh S., Radfar, Lida, Lewis, David, Stone, Donald U., Kaufman, C. Erick, Li, Shibo, Segal, Barbara, Wallace, Daniel J., Weisman, Michael H., Venuturupalli, Swamy, Kelly, Jennifer A., Pons‐Estel, Bernardo, Jonsson, Roland, Lu, Xianglan, Gottenberg, Jacques‐Eric, Anaya, Juan‐Manuel, Cunninghame‐Graham, Deborah S., Huang, Andrew J. W., Brennan, Michael T., Hughes, Pamela, Alevizos, Ilias, Miceli‐Richard, Corinne, Keystone, Edward C., Bykerk, Vivian P., Hirschfield, Gideon, Nordmark, Gunnel, Bucher, Sara Magnusson, Eriksson, Per, Omdal, Roald, Rhodus, Nelson L., Rischmueller, Maureen, Rohrer, Michael, Wahren‐Herlenius, Marie, Witte, Torsten, Alarcón‐Riquelme, Marta, Mariette, Xavier, Lessard, Christopher J., Harley, John B., Ng, Wan‐Fai, Rasmussen, Astrid, Sivils, Kathy L., and Scofield, R. Hal

Published
2017
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7. Complement C4 Copy Number Variation is Linked to SSA/Ro and SSB/La Autoantibodies in Systemic Inflammatory Autoimmune Diseases

Author

Lundtoft, Christian, Pucholt, Pascal, Martin, Myriam, Bianchi, Matteo, Lundstrom, Emeli, Eloranta, Maija-Leena, Sandling, Johanna K., Sjöwall, Christopher, Jonsen, Andreas, Gunnarsson, Iva, Rantapaa-Dahlqvist, Solbritt, Bengtsson, Anders A., Leonard, Dag, Baecklund, Eva, Jonsson, Roland, Hammenfors, Daniel, Forsblad-dElia, Helena, Eriksson, Per, Mandl, Thomas, Bucher, Sara Magnusson, Norheim, Katrine B., Johnsen, Svein Joar Auglaend, Omdal, Roald, Kvarnstrom, Marika, Wahren-Herlenius, Marie, Notarnicola, Antonella, Andersson, Helena, Molberg, Oyvind, Diederichsen, Louise Pyndt, Almlof, Jonas, Syvanen, Ann-Christine, Kozyrev, Sergey V, Lindblad-Toh, Kerstin, Nilsson, Bo, Blom, Anna M., Lundberg, Ingrid E., Nordmark, Gunnel, Diaz-Gallo, Lina Marcela, Svenungsson, Elisabet, Ronnblom, Lars, Lundtoft, Christian, Pucholt, Pascal, Martin, Myriam, Bianchi, Matteo, Lundstrom, Emeli, Eloranta, Maija-Leena, Sandling, Johanna K., Sjöwall, Christopher, Jonsen, Andreas, Gunnarsson, Iva, Rantapaa-Dahlqvist, Solbritt, Bengtsson, Anders A., Leonard, Dag, Baecklund, Eva, Jonsson, Roland, Hammenfors, Daniel, Forsblad-dElia, Helena, Eriksson, Per, Mandl, Thomas, Bucher, Sara Magnusson, Norheim, Katrine B., Johnsen, Svein Joar Auglaend, Omdal, Roald, Kvarnstrom, Marika, Wahren-Herlenius, Marie, Notarnicola, Antonella, Andersson, Helena, Molberg, Oyvind, Diederichsen, Louise Pyndt, Almlof, Jonas, Syvanen, Ann-Christine, Kozyrev, Sergey V, Lindblad-Toh, Kerstin, Nilsson, Bo, Blom, Anna M., Lundberg, Ingrid E., Nordmark, Gunnel, Diaz-Gallo, Lina Marcela, Svenungsson, Elisabet, and Ronnblom, Lars

Abstract

Objective Copy number variation of the C4 complement components, C4A and C4B, has been associated with systemic inflammatory autoimmune diseases. This study was undertaken to investigate whether C4 copy number variation is connected to the autoimmune repertoire in systemic lupus erythematosus (SLE), primary Sjogrens syndrome (SS), or myositis. Methods Using targeted DNA sequencing, we determined the copy number and genetic variants of C4 in 2,290 well-characterized Scandinavian patients with SLE, primary SS, or myositis and 1,251 healthy controls. Results A prominent relationship was observed between C4A copy number and the presence of SSA/SSB autoantibodies, which was shared between the 3 diseases. The strongest association was detected in patients with autoantibodies against both SSA and SSB and 0 C4A copies when compared to healthy controls (odds ratio [OR] 18.0 [95% confidence interval (95% CI) 10.2-33.3]), whereas a weaker association was seen in patients without SSA/SSB autoantibodies (OR 3.1 [95% CI 1.7-5.5]). The copy number of C4 correlated positively with C4 plasma levels. Further, a common loss-of-function variant in C4A leading to reduced plasma C4 was more prevalent in SLE patients with a low copy number of C4A. Functionally, we showed that absence of C4A reduced the individuals capacity to deposit C4b on immune complexes. Conclusion We show that a low C4A copy number is more strongly associated with the autoantibody repertoire than with the clinically defined disease entities. These findings may have implications for understanding the etiopathogenetic mechanisms of systemic inflammatory autoimmune diseases and for patient stratification when taking the genetic profile into account., Funding Agencies|Swedish Research Council for Medicine and Health; Swedish Rheumatism Association; Swedish Society of Medicine; Swedish Heart Lung Foundation; Stockholm County; Karolinska Institutet; Wallenberg Scholarship; King Gustav Vs 80-Year Foundation

Published
2022
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8. Strong Association of Combined Genetic Deficiencies in the Classical Complement Pathway With Risk of Systemic Lupus Erythematosus and Primary Sjögren's Syndrome

Author

Lundtoft, Christian, Sjöwall, Christopher, Rantapää‐Dahlqvist, Solbritt, Bengtsson, Anders A., Jönsen, Andreas, Pucholt, Pascal, Wu, Yee Ling, Lundström, Emeli, Eloranta, Maija-Leena, Gunnarsson, Iva, Baecklund, Eva, Jonsson, Roland, Hammenfors, Daniel, Forsblad‐d'Elia, Helena, Eriksson, Per, Mandl, Thomas, Bucher, Sara, Norheim, Katrine B., Auglaend Johnsen, Svein Joar, Omdal, Roald, Kvarnström, Marika, Wahren‐Herlenius, Marie, Truedsson, Lennart, Nilsson, Bo, Kozyrev, Sergey V., Bianchi, Matteo, Lindblad‐Toh, Kerstin, Yu, Chack‐Yung, Nordmark, Gunnel, Sandling, Johanna K., Svenungsson, Elisabet, Leonard, Dag, Rönnblom, Lars, Lundtoft, Christian, Sjöwall, Christopher, Rantapää‐Dahlqvist, Solbritt, Bengtsson, Anders A., Jönsen, Andreas, Pucholt, Pascal, Wu, Yee Ling, Lundström, Emeli, Eloranta, Maija-Leena, Gunnarsson, Iva, Baecklund, Eva, Jonsson, Roland, Hammenfors, Daniel, Forsblad‐d'Elia, Helena, Eriksson, Per, Mandl, Thomas, Bucher, Sara, Norheim, Katrine B., Auglaend Johnsen, Svein Joar, Omdal, Roald, Kvarnström, Marika, Wahren‐Herlenius, Marie, Truedsson, Lennart, Nilsson, Bo, Kozyrev, Sergey V., Bianchi, Matteo, Lindblad‐Toh, Kerstin, Yu, Chack‐Yung, Nordmark, Gunnel, Sandling, Johanna K., Svenungsson, Elisabet, Leonard, Dag, and Rönnblom, Lars

Abstract

Objective: Complete genetic deficiency of the complement component C2 is a strong risk factor for monogenic systemic lupus erythematosus (SLE), but whether heterozygous C2 deficiency adds to the risk of SLE or primary Sjögren's syndrome (SS) has not been studied systematically. This study was undertaken to investigate potential associations of heterozygous C2 deficiency and C4 copy number variation with clinical manifestations in patients with SLE and patients with primary SS. Methods: The presence of the common 28-bp C2 deletion rs9332736 and C4 copy number variation was examined in Scandinavian patients who had received a diagnosis of SLE (n = 958) or primary SS (n = 911) and in 2,262 healthy controls through the use of DNA sequencing. The concentration of complement proteins in plasma and classical complement function were analyzed in a subgroup of SLE patients. Results: Heterozygous C2 deficiency—when present in combination with a low C4A copy number—substantially increased the risk of SLE (odds ratio [OR] 10.2 [95% confidence interval (95% CI) 3.5–37.0]) and the risk of primary SS (OR 13.0 [95% CI 4.5–48.4]) when compared to individuals with 2 C4A copies and normal C2. For patients heterozygous for rs9332736 with 1 C4A copy, the median age at diagnosis was 7 years earlier in patients with SLE and 12 years earlier in patients with primary SS when compared to patients with normal C2. Reduced C2 levels in plasma (P = 2 × 10−9) and impaired function of the classical complement pathway (P = 0.03) were detected in SLE patients with heterozygous C2 deficiency. Finally, in a primary SS patient homozygous for C2 deficiency, we observed low levels of anti–Scl-70, which suggests a risk of developing systemic sclerosis or potential overlap between primary SS and other systemic autoimmune diseases. Coclusions: We demonstrate that a genetic pattern involving partial deficiencies of C2 and C4A in the classical complement pathway is a strong risk factor for SLE and for primary

Published
2022
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9. Author Correction: Genome-wide association study identifies Sjogrens risk loci with functional implications in immune and glandular cells (vol 13, 4287, 2022)

Author

Khatri, Bhuwan, Tessneer, Kandice L., Rasmussen, Astrid, Aghakhanian, Farhang, Reksten, Tove Ragna, Adler, Adam, Alevizos, Ilias, Anaya, Juan-Manuel, Aqrawi, Lara A., Baecklund, Eva, Brun, Johan G., Bucher, Sara Magnusson, Eloranta, Maija-Leena, Engelke, Fiona, Forsblad-dElia, Helena, Glenn, Stuart B., Hammenfors, Daniel, Imgenberg-Kreuz, Juliana, Jensen, Janicke Liaaen, Johnsen, Svein Joar Auglaend, Jonsson, Malin V., Kvarnstrom, Marika, Kelly, Jennifer A., Li, He, Mandl, Thomas, Martin, Javier, Nocturne, Gaetane, Norheim, Katrine Braekke, Palm, Oyvind, Skarstein, Kathrine, Stolarczyk, Anna M., Taylor, Kimberly E., Teruel, Maria, Theander, Elke, Venuturupalli, Swamy, Wallace, Daniel J., Grundahl, Kiely M., Hefner, Kimberly S., Radfar, Lida, Lewis, David M., Stone, Donald U., Kaufman, C. Erick, Brennan, Michael T., Guthridge, Joel M., James, Judith A., Scofield, R. Hal, Gaffney, Patrick M., Criswell, Lindsey A., Jonsson, Roland, Eriksson, Per, Bowman, Simon J., Omdal, Roald, Ronnblom, Lars, Warner, Blake, Rischmueller, Maureen, Witte, Torsten, Farris, A. Darise, Mariette, Xavier, Alarcon-Riquelme, Marta E., Shiboski, Caroline H., Wahren-Herlenius, Marie, Ng, Wan-Fai, Sivils, Kathy L., Adrianto, Indra, Nordmark, Gunnel, Lessard, Christopher J., Khatri, Bhuwan, Tessneer, Kandice L., Rasmussen, Astrid, Aghakhanian, Farhang, Reksten, Tove Ragna, Adler, Adam, Alevizos, Ilias, Anaya, Juan-Manuel, Aqrawi, Lara A., Baecklund, Eva, Brun, Johan G., Bucher, Sara Magnusson, Eloranta, Maija-Leena, Engelke, Fiona, Forsblad-dElia, Helena, Glenn, Stuart B., Hammenfors, Daniel, Imgenberg-Kreuz, Juliana, Jensen, Janicke Liaaen, Johnsen, Svein Joar Auglaend, Jonsson, Malin V., Kvarnstrom, Marika, Kelly, Jennifer A., Li, He, Mandl, Thomas, Martin, Javier, Nocturne, Gaetane, Norheim, Katrine Braekke, Palm, Oyvind, Skarstein, Kathrine, Stolarczyk, Anna M., Taylor, Kimberly E., Teruel, Maria, Theander, Elke, Venuturupalli, Swamy, Wallace, Daniel J., Grundahl, Kiely M., Hefner, Kimberly S., Radfar, Lida, Lewis, David M., Stone, Donald U., Kaufman, C. Erick, Brennan, Michael T., Guthridge, Joel M., James, Judith A., Scofield, R. Hal, Gaffney, Patrick M., Criswell, Lindsey A., Jonsson, Roland, Eriksson, Per, Bowman, Simon J., Omdal, Roald, Ronnblom, Lars, Warner, Blake, Rischmueller, Maureen, Witte, Torsten, Farris, A. Darise, Mariette, Xavier, Alarcon-Riquelme, Marta E., Shiboski, Caroline H., Wahren-Herlenius, Marie, Ng, Wan-Fai, Sivils, Kathy L., Adrianto, Indra, Nordmark, Gunnel, and Lessard, Christopher J.

Published
2022
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10. Genetic and clinical basis for two distinct subtypes of primary Sjögren's syndrome

Author

Thorlacius, Guðný Ella, Hultin-Rosenberg, Lina, Sandling, Johanna K., Bianchi, Matteo, Imgenberg-Kreuz, Juliana, Pucholt, Pascal, Theander, Elke, Kvarnström, Marika, Forsblad-D'elia, Helena, Bucher, Sara Magnusson, Norheim, Katrine B., Johnsen, Svein Joar Auglænd, Hammenfors, Daniel, Skarstein, Kathrine, Jonsson, Malin V., Baecklund, Eva, Aqrawi, Lara A., Jensen, Janicke Liaaen, Palm, Øyvind, Morris, Andrew P., Alexsson, Andrei, Backlin, Carin, Rönnblom, Lars, Vasaitis, Lilian, Eloranta, Maija Leena, Syvänen, Ann Christine, Mathioudaki, Argyri, Farias, Fabiana H.G., Meadows, Jennifer, Nordin, Jessika, Lindblad-Toh, Kerstin, Björk, Albin, Lundberg, Ingrid E., Sepúlveda, Jorge I.Ramírez, Wahren-Herlenius, Marie, Eriksson, Daniel, Eriksson, Per, Sjöwall, Christopher, Mandl, Thomas, Rantapaä¨-Dahlqvist, Solbritt, Brokstad, Karl A., Jonsson, Roland, Appel, Silke, Brun, Johan G., Norheim, Katrine Brække, Omdal, Roald, Aqrawi, Lara Adnan, Pielberg, Gerli Rosengren, Murén, Eva, Karlsson, Åsa, Andersson, Göran, Ahlgren, Kerstin M., Lobell, Anna, Söderkvist, Peter, Kämpe, Olle, Landegren, Nils, Meadows, Jennifer R.S., Lind, Lars, and Nordmark, Gunnel

Subjects
musculoskeletal diseases, stomatognathic diseases, stomatognathic system, gene polymorphism, autoantibodies, autoimmunity, Sjögren's syndrome, eye diseases
Abstract

Objectives: Clinical presentation of primary Sjögren's syndrome (pSS) varies considerably. A shortage of evidence-based objective markers hinders efficient drug development and most clinical trials have failed to reach primary endpoints. Methods: We performed a multicentre study to identify patient subgroups based on clinical, immunological and genetic features. Targeted DNA sequencing of 1853 autoimmune-related loci was performed. After quality control, 918 patients with pSS, 1264 controls and 107 045 single nucleotide variants remained for analysis. Replication was performed in 177 patients with pSS and 7672 controls. Results: We found strong signals of association with pSS in the HLA region. Principal component analysis of clinical data distinguished two patient subgroups defined by the presence of SSA/SSB antibodies. We observed an unprecedented high risk of pSS for an association in the HLA-DQA1 locus of odds ratio 6.10 (95% CI: 4.93, 7.54, P=2.2×10-62) in the SSA/SSB-positive subgroup, while absent in the antibody negative group. Three independent signals within the MHC were observed. The two most significant variants in MHC class I and II respectively, identified patients with a higher risk of hypergammaglobulinaemia, leukopenia, anaemia, purpura, major salivary gland swelling and lymphadenopathy. Replication confirmed the association with both MHC class I and II signals confined to SSA/SSB antibody positive pSS. Conclusion: Two subgroups of patients with pSS with distinct clinical manifestations can be defined by the presence or absence of SSA/SSB antibodies and genetic markers in the HLA locus. These subgroups should be considered in clinical follow-up, drug development and trial outcomes, for the benefit of both subgroups.

Published
2021

11. Genetic and clinical basis for two distinct subtypes of primary Sjogrens syndrome

Author

Thorlacius, Gudny Ella, Hultin-Rosenberg, Lina, Sandling, Johanna K., Bianchi, Matteo, Imgenberg-Kreuz, Juliana, Pucholt, Pascal, Theander, Elke, Kvarnstrom, Marika, Forsblad-dElia, Helena, Bucher, Sara Magnusson, Norheim, Katrine B., Johnsen, Svein Joar Auglaend, Hammenfors, Daniel, Skarstein, Kathrine, Jonsson, Malin V, Baecklund, Eva, Aqrawi, Lara A., Jensen, Janicke Liaaen, Palm, Oyvind, Morris, Andrew P., Meadows, Jennifer R. S., Rantapaa-Dahlqvist, Solbritt, Mandl, Thomas, Eriksson, Per, Lind, Lars, Omdal, Roald, Jonsson, Roland, Lindblad-Toh, Kerstin, Ronnblom, Lars, Wahren-Herlenius, Marie, Nordmark, Gunnel, Thorlacius, Gudny Ella, Hultin-Rosenberg, Lina, Sandling, Johanna K., Bianchi, Matteo, Imgenberg-Kreuz, Juliana, Pucholt, Pascal, Theander, Elke, Kvarnstrom, Marika, Forsblad-dElia, Helena, Bucher, Sara Magnusson, Norheim, Katrine B., Johnsen, Svein Joar Auglaend, Hammenfors, Daniel, Skarstein, Kathrine, Jonsson, Malin V, Baecklund, Eva, Aqrawi, Lara A., Jensen, Janicke Liaaen, Palm, Oyvind, Morris, Andrew P., Meadows, Jennifer R. S., Rantapaa-Dahlqvist, Solbritt, Mandl, Thomas, Eriksson, Per, Lind, Lars, Omdal, Roald, Jonsson, Roland, Lindblad-Toh, Kerstin, Ronnblom, Lars, Wahren-Herlenius, Marie, and Nordmark, Gunnel

Abstract

Objectives. Clinical presentation of primary Sjogrens syndrome (pSS) varies considerably. A shortage of evidence-based objective markers hinders efficient drug development and most clinical trials have failed to reach primary endpoints. Methods. We performed a multicentre study to identify patient subgroups based on clinical, immunological and genetic features. Targeted DNA sequencing of 1853 autoimmune-related loci was performed. After quality control, 918 patients with pSS, 1264 controls and 107 045 single nucleotide variants remained for analysis. Replication was performed in 177 patients with pSS and 7672 controls. Results. We found strong signals of association with pSS in the HLA region. Principal component analysis of clinical data distinguished two patient subgroups defined by the presence of SSA/SSB antibodies. We observed an unprecedented high risk of pSS for an association in the HLA-DQA1 locus of odds ratio 6.10 (95% CI: 4.93, 7.54, P=2.2 x 10(-62)) in the SSA/SSB-positive subgroup, while absent in the antibody negative group. Three independent signals within the MHC were observed. The two most significant variants in MHC class I and II respectively, identified patients with a higher risk of hypergammaglobulinaemia, leukopenia, anaemia, purpura, major salivary gland swelling and lymphadenopathy. Replication confirmed the association with both MHC class I and II signals confined to SSA/SSB antibody positive pSS. Conclusion. Two subgroups of patients with pSS with distinct clinical manifestations can be defined by the presence or absence of SSA/SSB antibodies and genetic markers in the HLA locus. These subgroups should be considered in clinical follow-up, drug development and trial outcomes, for the benefit of both subgroups., Funding Agencies|Swedish Research Council for Medicine and Health; Swedish Rheumatism Association; King Gustav Vs 80-year Foundation; Knut and Alice Wallenberg FoundationKnut & Alice Wallenberg Foundation; AstraZeneca-Science for Life Laboratory Research Collaboration grant (DISSECT)

Published
2021
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12. Sustenance.

Author

Bucher, Sara

Subjects
TWILIGHT, OMELETS, PUMPKINS, ORPHANS, SNEEZING
Abstract

The article, titled "Sustenance," is a personal reflection on the author's experiences in Newtown, a neighborhood in an unidentified location. The author describes the atmosphere of the area, including its rainy weather and the perception of it as a gloomy place. The author also recounts a visit to a hospital, where they receive compassionate advice from a nurse about taking medication. The article then shifts to a scene with the author and a person named Mira, discussing their plans for the next day. The author expresses fear and gratitude, but the conversation remains silent. The article concludes with the author and Mira in bed, with the author sharing a macabre fact and hoping for a joke, but Mira responds with warmth and mentions pumpkin soup. The author, Sara Bucher, holds a Master of Creative Writing and currently resides in Pōneke. [Extracted from the article]

Published
2024

13. Genetic and clinical basis for two distinct subtypes of primary Sjögren's syndrome

Author

Thorlacius, Gudny Ella, Hultin-Rosenberg, Lina, Sandling, Johanna K., Bianchi, Matteo, Imgenberg-Kreuz, Juliana, Theander, Elke, Kvarnström, Marika, Forsblad-d’Elia, Helena, Bucher, Sara Magnusson, Norheim, Katrine Brække, Johnsen, Svein Joar Auglænd, Hammenfors, Sten Daniel, Skarstein, Kathrine, Jonsson, Malin V, Bäcklund, Eva, consortium, the DISSECT, meadows, jennifer r, Rantapää-Dahlqvist, Solbritt, Mandl, Thomas, Eriksson, Per, Omdal, Roald, Jonsson, Sten Ture Roland, Lindblad-Toh, Kerstin, Rönnblom, Lars, Wahren-Herlenius, Marie, and Nordmark, Gunnel

Subjects
musculoskeletal diseases, stomatognathic diseases, stomatognathic system, eye diseases
Abstract

Objectives Clinical presentation of primary Sjögren’s syndrome (pSS) varies considerably. A shortage of evidence-based objective markers hinders efficient drug development and most clinical trials have failed to reach primary endpoints. Methods We performed a multicentre study to identify patient subgroups based on clinical, immunological and genetic features. Targeted DNA sequencing of 1853 autoimmune-related loci was performed. After quality control, 918 patients with pSS, 1264 controls and 107 045 single nucleotide variants remained for analysis. Replication was performed in 177 patients with pSS and 7672 controls. Results We found strong signals of association with pSS in the HLA region. Principal component analysis of clinical data distinguished two patient subgroups defined by the presence of SSA/SSB antibodies. We observed an unprecedented high risk of pSS for an association in the HLA-DQA1 locus of odds ratio 6.10 (95% CI: 4.93, 7.54, P=2.2×10−62) in the SSA/SSB-positive subgroup, while absent in the antibody negative group. Three independent signals within the MHC were observed. The two most significant variants in MHC class I and II respectively, identified patients with a higher risk of hypergammaglobulinaemia, leukopenia, anaemia, purpura, major salivary gland swelling and lymphadenopathy. Replication confirmed the association with both MHC class I and II signals confined to SSA/SSB antibody positive pSS. Conclusion Two subgroups of patients with pSS with distinct clinical manifestations can be defined by the presence or absence of SSA/SSB antibodies and genetic markers in the HLA locus. These subgroups should be considered in clinical follow-up, drug development and trial outcomes, for the benefit of both subgroups. publishedVersion

Published
2020

14. Cigarette smoking patterns preceding primary Sjögren's syndrome

Author

Mofors, Johannes, Björk, Albin, Richardsdotter Andersson, Elina, Kvarnström, Marika, Forsblad d'Elia, Helena, Magnusson-Bucher, Sara, Padyukov, Leonid, Kockum, Ingrid, Hillert, Jan, Eriksson, Per, Mandl, Thomas, Nordmark, Gunnel, Alfredsson, Lars, Wahren-Herlenius, Marie, Mofors, Johannes, Björk, Albin, Richardsdotter Andersson, Elina, Kvarnström, Marika, Forsblad d'Elia, Helena, Magnusson-Bucher, Sara, Padyukov, Leonid, Kockum, Ingrid, Hillert, Jan, Eriksson, Per, Mandl, Thomas, Nordmark, Gunnel, Alfredsson, Lars, and Wahren-Herlenius, Marie

Abstract

Background Cigarette smoking is a well-established risk factor for several autoimmune diseases, but its role in primary Sjögren’s syndrome (pSS) remains unclear. Here, we investigated the association between cigarette smoking and subsequent development of pSS. Methods Information on smoking habits was collected from lifestyle habit questionnaires of patients with pSS (n=815) and a matched control group (n=4425) for a case–control study. Differences in smoking exposure were analysed by conditional logistic regression. Potential interactions between smoking and risk-associated human leucocyte antigens (HLA) were assessed by multivariate regression. Results The fraction of patients with pSS having ever smoked prior to diagnosis was lower than in controls (OR 0.67, 95% CI 0.55 to 0.81). Current smoking at diagnosis was also less prevalent in cases (OR 0.37, 95% CI 0.26 to 0.53). However, period prevalence of smoking during early adulthood was not statistically different from controls (OR 0.89, 95% CI 0.66 to 1.22) but markedly decreased over time. This was partly due to patients being more prone to stop smoking, starting already 30 years prior to diagnosis (OR 2.01, 95% CI 1.22 to 3.30). Smoking patterns were also stratified by autoantibody status, yielding similar estimates. No interaction effects between HLA-DRB1 haplotypes and smoking were observed. Conclusion The observed smoking patterns indicate that individuals who develop pSS smoke equally much as the general population during early life but are then more prone to stop. The data can be interpreted as smoking conferring protective effects, or reflecting early symptoms of pSS that affect smoking habits, emphasising the slow, progressive development of the disease.

Published
2020
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15. Increased risk of multiple myeloma in primary Sjogren's syndrome is limited to individuals with Ro/SSA and La/SSB autoantibodies

Author

Mofors, Johannes, Björk, Albin, Smedby, Karin E., Kvarnström, Marika, Forsblad-d'Elia, Helena, Magnusson-Bucher, Sara, Eriksson, Per, Mandl, Thomas, Baecklund, Eva, Nordmark, Gunnel, Wahren-Herlenius, Marie, Mofors, Johannes, Björk, Albin, Smedby, Karin E., Kvarnström, Marika, Forsblad-d'Elia, Helena, Magnusson-Bucher, Sara, Eriksson, Per, Mandl, Thomas, Baecklund, Eva, Nordmark, Gunnel, and Wahren-Herlenius, Marie

Published
2020
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16. Cigarette smoking patterns preceding primary Sjögren’s syndrome

Author

Mofors, Johannes, primary, Björk, Albin, additional, Richardsdotter Andersson, Elina, additional, Kvarnström, Marika, additional, Forsblad d’Elia, Helena, additional, Magnusson-Bucher, Sara, additional, Padyukov, Leonid, additional, Kockum, Ingrid, additional, Hillert, Jan, additional, Eriksson, Per, additional, Mandl, Thomas, additional, Nordmark, Gunnel, additional, Alfredsson, Lars, additional, and Wahren-Herlenius, Marie, additional

Published
2020
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17. Increased risk of multiple myeloma in primary Sjögren’s syndrome is limited to individuals with Ro/SSA and La/SSB autoantibodies

Author

Mofors, Johannes, primary, Björk, Albin, additional, Smedby, Karin E, additional, Kvarnström, Marika, additional, Forsblad-d'Elia, Helena, additional, Magnusson-Bucher, Sara, additional, Eriksson, Per, additional, Mandl, Thomas, additional, Baecklund, Eva, additional, Nordmark, Gunnel, additional, and Wahren-Herlenius, Marie, additional

Published
2019
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18. Primary Sjögren's syndrome increases the risk of cardiovascular events, with the highest risk in SSA/SSB autoantibody positive patients

Author

Mofors, Johannes, Westermark, Linnea, Bjork, Albin, Kvarnstrom, Marika, Forsblad-d'Elia, Helena, Bucher, Sara Magnusson, Eriksson, Per, Mandl, Thomas, Wahren-Herlenius, Marie, Nordmark, Gunnel, Mofors, Johannes, Westermark, Linnea, Bjork, Albin, Kvarnstrom, Marika, Forsblad-d'Elia, Helena, Bucher, Sara Magnusson, Eriksson, Per, Mandl, Thomas, Wahren-Herlenius, Marie, and Nordmark, Gunnel

Published
2018

19. Genetic basis and clinical evidence for two variants of primary Sjögren's syndrome with distinct outcomes

Author

Thorlacius, Gudny Ella, Hultin-Rosenberg, Lina, Sandling, Johanna K., Imgenberg-Kreuz, Juliana, Theander, Elke, Kvarnstrom, Marika, Forsblad-d'Elia, Helena, Bucher, Sara Magnusson, Norheim, Katrine Braekke, Johnsen, Svein Joar, Hammenfors, Daniel, Skarstein, Kathrine, Jonsson, Malin V., Baecklund, Eva, Mandl, Thomas, Eriksson, Per, Omdal, Roald, Jonsson, Roland, Lindblad-Toh, Kerstin, Rönnblom, Lars, Wahren-Herlenius, Marie, Nordmark, Gunnel, Thorlacius, Gudny Ella, Hultin-Rosenberg, Lina, Sandling, Johanna K., Imgenberg-Kreuz, Juliana, Theander, Elke, Kvarnstrom, Marika, Forsblad-d'Elia, Helena, Bucher, Sara Magnusson, Norheim, Katrine Braekke, Johnsen, Svein Joar, Hammenfors, Daniel, Skarstein, Kathrine, Jonsson, Malin V., Baecklund, Eva, Mandl, Thomas, Eriksson, Per, Omdal, Roald, Jonsson, Roland, Lindblad-Toh, Kerstin, Rönnblom, Lars, Wahren-Herlenius, Marie, and Nordmark, Gunnel

Published
2018

20. Infections predispose to developing primary Sjögren's syndrome

Author

Mofors, Johannes, Arkema, Elisabeth V., Westermark, Linnea, Bjorki, Albin, Kvarnstrom, Marika, Forsblad-d'Elia, Helena, Bucher, Sara Magnusson, Eriksson, Per, Mandl, Thomas, Nordmark, Gunnel, Wahren-Herlenius, Marie, Mofors, Johannes, Arkema, Elisabeth V., Westermark, Linnea, Bjorki, Albin, Kvarnstrom, Marika, Forsblad-d'Elia, Helena, Bucher, Sara Magnusson, Eriksson, Per, Mandl, Thomas, Nordmark, Gunnel, and Wahren-Herlenius, Marie

Published
2018

21. Cigarette smoking is a risk factor for developing primary Sjögren's syndrome with Ro/SSA and La/SSB autoantibodies

Author

Björk, Albin, Mofors, Johannes, Kvarnström, Marika, Forsblad-d'Elia, Helena, Bucher, Sara Magnusson, Hillert, Jan, Eriksson, Per, Mandl, Thomas, Nordmark, Gunnel, Alfredsson, Lars, Wahren-Herlenius, Marie, Björk, Albin, Mofors, Johannes, Kvarnström, Marika, Forsblad-d'Elia, Helena, Bucher, Sara Magnusson, Hillert, Jan, Eriksson, Per, Mandl, Thomas, Nordmark, Gunnel, Alfredsson, Lars, and Wahren-Herlenius, Marie

Published
2018

22. Correction: Klinefelters syndrome (47,XXY) is in excess among men with Sjogrens syndrome (vol 168, pg 25, 2016)

Author

Harris, Valerie M., Sharma, Rohan, Cavett, Joshua, Kurien, Biji T., Liu, Ke, Koelsch, Kristi A., Rasmussen, Astrid, Radfar, Lida, Lewis, David, Stone, Donald U., Kaufman, C. Erick, Li, Shibo, Segal, Barbara, Wallace, Daniel J., Weisman, Michael H., Venuturupalli, Swamy, Kelly, Jennifer A., Alarcon-Riquelme, Marta E., Pons-Estel, Bernardo, Jonsson, Roland, Lu, Xianglan, Gottenberg, Jacques-Eric, Anaya, Juan-Manuel, Cunninghame-Graham, Deborah S., Huang, Andrew J. W., Brennan, Michael T., Hughes, Pamela, Alevizos, Ilias, Miceli-Richard, Corinne, Keystone, Edward C., Bykerk, Vivian P., Hirschfield, Gideon, Xie, Gang, Siminovitch, Katherine A., Ng, Wan-Fai, Nordmark, Gunnel, Bucher, Sara Magnusson, Eriksson, Per, Omdal, Roald, Rhodus, Nelson L., Rischmueller, Maureen, Rohrer, Michael, Wahren-Herlenius, Marie, Witte, Torsten, Mariette, Xavier, Lessard, Christopher J., Harley, John B., Sivils, Kathy L., Scofield, R. Hal, Harris, Valerie M., Sharma, Rohan, Cavett, Joshua, Kurien, Biji T., Liu, Ke, Koelsch, Kristi A., Rasmussen, Astrid, Radfar, Lida, Lewis, David, Stone, Donald U., Kaufman, C. Erick, Li, Shibo, Segal, Barbara, Wallace, Daniel J., Weisman, Michael H., Venuturupalli, Swamy, Kelly, Jennifer A., Alarcon-Riquelme, Marta E., Pons-Estel, Bernardo, Jonsson, Roland, Lu, Xianglan, Gottenberg, Jacques-Eric, Anaya, Juan-Manuel, Cunninghame-Graham, Deborah S., Huang, Andrew J. W., Brennan, Michael T., Hughes, Pamela, Alevizos, Ilias, Miceli-Richard, Corinne, Keystone, Edward C., Bykerk, Vivian P., Hirschfield, Gideon, Xie, Gang, Siminovitch, Katherine A., Ng, Wan-Fai, Nordmark, Gunnel, Bucher, Sara Magnusson, Eriksson, Per, Omdal, Roald, Rhodus, Nelson L., Rischmueller, Maureen, Rohrer, Michael, Wahren-Herlenius, Marie, Witte, Torsten, Mariette, Xavier, Lessard, Christopher J., Harley, John B., Sivils, Kathy L., and Scofield, R. Hal

Abstract

n/a, Funding Agencies|BLRD VA [I01 BX001451]

Published
2018
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23. Corrigendum to “Klinefelter's syndrome (47,XXY) is in excess among men with Sjögren's syndrome” [Clin. Immunol. 168 (2016) 25–29]

Author

Harris, Valerie M., primary, Sharma, Rohan, additional, Cavett, Joshua, additional, Kurien, Biji T., additional, Liu, Ke, additional, Koelsch, Kristi A., additional, Rasmussen, Astrid, additional, Radfar, Lida, additional, Lewis, David, additional, Stone, Donald U., additional, Kaufman, C. Erick, additional, Li, Shibo, additional, Segal, Barbara, additional, Wallace, Daniel J., additional, Weisman, Michael H., additional, Venuturupalli, Swamy, additional, Kelly, Jennifer A., additional, Alarcon-Riquelme, Marta E., additional, Pons-Estel, Bernardo, additional, Jonsson, Roland, additional, Lu, Xianglan, additional, Gottenberg, Jacques-Eric, additional, Anaya, Juan-Manuel, additional, Cunninghame-Graham, Deborah S., additional, Huang, Andrew J.W., additional, Brennan, Michael T., additional, Hughes, Pamela, additional, Alevizos, Ilias, additional, Miceli-Richard, Corinne, additional, Keystone, Edward C., additional, Bykerk, Vivian P., additional, Hirschfield, Gideon, additional, Xie, Gang, additional, Siminovitch, Katherine A., additional, Ng, Wan-Fai, additional, Nordmark, Gunnel, additional, Bucher, Sara Magnusson, additional, Eriksson, Per, additional, Omdal, Roald, additional, Rhodus, Nelson L., additional, Rischmueller, Maureen, additional, Rohrer, Michael, additional, Wahren-Herlenius, Marie, additional, Witte, Torsten, additional, Mariette, Xavier, additional, Lessard, Christopher J., additional, Harley, John B., additional, Sivils, Kathy L., additional, and Scofield, R. Hal, additional

Published
2018
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24. Difference in Clinical Presentation between Female and Male Patients with Primary Sjogren's Syndrome at Diagnosis and in Long-Term Follow-up

Author

Ramirez, Jorge, Kvarnstrom, Marika, Brauner, Susanna, Baldini, Chiara, Eriksson, Per, Mandl, Thomas, Norheim, Katrine Braekke, Johnsen, Svein Joar, Hammenfors, Daniel S., Jonsson, Malin V., Skarstein, Kathrine, Brun, Johan G., Rönnblom, Lars, D'Elia, Helena Forsblad, Bucher, Sara Magnusson, Theander, Elke, Omdal, Roald, Jonsson, Roland, Nordmark, Gunnel, Wahren-Herlenius, Marie, Ramirez, Jorge, Kvarnstrom, Marika, Brauner, Susanna, Baldini, Chiara, Eriksson, Per, Mandl, Thomas, Norheim, Katrine Braekke, Johnsen, Svein Joar, Hammenfors, Daniel S., Jonsson, Malin V., Skarstein, Kathrine, Brun, Johan G., Rönnblom, Lars, D'Elia, Helena Forsblad, Bucher, Sara Magnusson, Theander, Elke, Omdal, Roald, Jonsson, Roland, Nordmark, Gunnel, and Wahren-Herlenius, Marie

Published
2017

25. Rare X Chromosome Abnormalities in Systemic Lupus Erythematosus and Sjögren's Syndrome

Author

Sharma, Rohan, Harris, Valerie M., Cavett, Joshua, Kurien, Biji T., Liu, Ke, Koelsch, Kristi A., Fayaaz, Anum, Chaudhari, Kaustubh S., Radfar, Lida, Lewis, David, Stone, Donald U., Kaufman, C. Erick, Li, Shibo, Segal, Barbara, Wallace, Daniel J., Weisman, Michael H., Venuturupalli, Swamy, Kelly, Jennifer A., Pons-Estel, Bernardo, Jonsson, Roland, Lu, Xianglan, Gottenberg, Jacques-Eric, Anaya, Juan-Manuel, Cunninghame-Graham, Deborah S., Huang, Andrew J. W., Brennan, Michael T., Hughes, Pamela, Alevizos, Ilias, Miceli-Richard, Corinne, Keystone, Edward C., Bykerk, Vivian P., Hirschfield, Gideon, Nordmark, Gunnel, Bucher, Sara Magnusson, Eriksson, Per, Omdal, Roald, Rhodus, Nelson L., Rischmueller, Maureen, Rohrer, Michael, Wahren-Herlenius, Marie, Witte, Torsten, Alarcon-Riquelme, Marta, Mariette, Xavier, Lessard, Christopher J., Harley, John B., Ng, Wan-Fai, Rasmussen, Astrid, Sivils, Kathy L., Scofield, R. Hal, Sharma, Rohan, Harris, Valerie M., Cavett, Joshua, Kurien, Biji T., Liu, Ke, Koelsch, Kristi A., Fayaaz, Anum, Chaudhari, Kaustubh S., Radfar, Lida, Lewis, David, Stone, Donald U., Kaufman, C. Erick, Li, Shibo, Segal, Barbara, Wallace, Daniel J., Weisman, Michael H., Venuturupalli, Swamy, Kelly, Jennifer A., Pons-Estel, Bernardo, Jonsson, Roland, Lu, Xianglan, Gottenberg, Jacques-Eric, Anaya, Juan-Manuel, Cunninghame-Graham, Deborah S., Huang, Andrew J. W., Brennan, Michael T., Hughes, Pamela, Alevizos, Ilias, Miceli-Richard, Corinne, Keystone, Edward C., Bykerk, Vivian P., Hirschfield, Gideon, Nordmark, Gunnel, Bucher, Sara Magnusson, Eriksson, Per, Omdal, Roald, Rhodus, Nelson L., Rischmueller, Maureen, Rohrer, Michael, Wahren-Herlenius, Marie, Witte, Torsten, Alarcon-Riquelme, Marta, Mariette, Xavier, Lessard, Christopher J., Harley, John B., Ng, Wan-Fai, Rasmussen, Astrid, Sivils, Kathy L., and Scofield, R. Hal

Abstract

Objective: Sjögren's syndrome (SS) and systemic lupus erythematosus (SLE) are related by clinical and serologic manifestations as well as genetic risks. Both diseases are more commonly found in women than in men, at a ratio of similar to 10 to 1. Common X chromosome aneuploidies, 47,XXY and 47,XXX, are enriched among men and women, respectively, in either disease, suggesting a dose effect on the X chromosome. Methods: We examined cohorts of SS and SLE patients by constructing intensity plots of X chromosome single-nucleotide polymorphism alleles, along with determining the karyotype of selected patients. Results: Among similar to 2,500 women with SLE, we found 3 patients with a triple mosaic, consisting of 45,X/46,XX/47,XXX. Among similar to 2,100 women with SS, 1 patient had 45,X/46,XX/47,XXX, with a triplication of the distal p arm of the X chromosome in the 47,XXX cells. Neither the triple mosaic nor the partial triplication was found among the controls. In another SS cohort, we found a mother/daughter pair with partial triplication of this same region of the X chromosome. The triple mosaic occurs in similar to 1 in 25,000-50,000 live female births, while partial triplications are even rarer. Conclusion: Very rare X chromosome abnormalities are present among patients with either SS or SLE and may inform the location of a gene(s) that mediates an X dose effect, as well as critical cell types in which such an effect is operative.

Published
2017
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26. Long-term follow-up in primary Sjögren's syndrome reveals differences in clinical presentation between female and male patients

Author

Sepulveda, Jorge I. Ramirez, Kvarnstrom, Marika, Eriksson, Per, Mandl, Thomas, Norheim, Katrine Braekke, Johnsen, Svein Joar, Hammenfors, Daniel, Jonsson, Malin V., Skarstein, Kathrine, Brun, Johan G., Rönnblom, Lars, Forsblad-d'Elia, Helena, Bucher, Sara Magnusson, Baecklund, Eva, Theander, Elke, Omdal, Roald, Jonsson, Roland, Nordmark, Gunnel, Wahren-Herlenius, Marie, Sepulveda, Jorge I. Ramirez, Kvarnstrom, Marika, Eriksson, Per, Mandl, Thomas, Norheim, Katrine Braekke, Johnsen, Svein Joar, Hammenfors, Daniel, Jonsson, Malin V., Skarstein, Kathrine, Brun, Johan G., Rönnblom, Lars, Forsblad-d'Elia, Helena, Bucher, Sara Magnusson, Baecklund, Eva, Theander, Elke, Omdal, Roald, Jonsson, Roland, Nordmark, Gunnel, and Wahren-Herlenius, Marie

Abstract

Background: Despite men being less prone to develop autoimmune diseases, male sex has been associated with a more severe disease course in several systemic autoimmune diseases. In the present study, we aimed to investigate differences in the clinical presentation of primary Sjogren's syndrome (pSS) between the sexes and establish whether male sex is associated with a more severe form of long-term pSS. Methods: Our study population included 967 patients with pSS (899 females and 68 males) from Scandinavian clinical centers. The mean follow-up time (years) was 8.8 +/- 7.6 for women and 8.5 +/- 6.2 for men (ns). Clinical data including serological and hematological parameters and glandular and extraglandular manifestations were compared between men and women. Results: Male patient serology was characterized by more frequent positivity for anti-Ro/SSA and anti-La/SSB (p = 0. 02), and ANA (p = 0.02). Further, men with pSS were more frequently diagnosed with interstitial lung disease (p = 0. 008), lymphadenopathy (p = 0.04) and lymphoma (p = 0.007). Conversely, concomitant hypothyroidism was more common among female patients (p = 0.009). Conclusions: We observe enhanced serological responses and higher frequencies of lymphoma-related extraglandular manifestations in men with pSS. Notably, lymphoma itself was also significantly more common in men. These observations may reflect an aggravated immune activation and a more severe pathophysiological state in male patients with pSS and indicate a personalized managing of the disease due to the influence of the sex of patients with pSS., Jennifer Meadows is a member of the DISSECT consortium.

Published
2017
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27. Long-term follow-up in primary Sjogrens syndrome reveals differences in clinical presentation between female and male patients

Author

Ramirez Sepulveda, Jorge I., Kvarnstrom, Marika, Eriksson, Per, Mandl, Thomas, Braekke Norheim, Katrine, Joar Johnsen, Svein, Hammenfors, Daniel, Jonsson, Malin V., Skarstein, Kathrine, Brun, Johan G., Ronnblom, Lars, Forsblad-dElia, Helena, Magnusson Bucher, Sara, Baecklund, Eva, Theander, Elke, Omdal, Roald, Jonsson, Roland, Nordmark, Gunnel, Wahren-Herlenius, Marie, Ramirez Sepulveda, Jorge I., Kvarnstrom, Marika, Eriksson, Per, Mandl, Thomas, Braekke Norheim, Katrine, Joar Johnsen, Svein, Hammenfors, Daniel, Jonsson, Malin V., Skarstein, Kathrine, Brun, Johan G., Ronnblom, Lars, Forsblad-dElia, Helena, Magnusson Bucher, Sara, Baecklund, Eva, Theander, Elke, Omdal, Roald, Jonsson, Roland, Nordmark, Gunnel, and Wahren-Herlenius, Marie

Abstract

Background: Despite men being less prone to develop autoimmune diseases, male sex has been associated with a more severe disease course in several systemic autoimmune diseases. In the present study, we aimed to investigate differences in the clinical presentation of primary Sjogrens syndrome (pSS) between the sexes and establish whether male sex is associated with a more severe form of long-term pSS. Methods: Our study population included 967 patients with pSS (899 females and 68 males) from Scandinavian clinical centers. The mean follow-up time (years) was 8.8 +/- 7.6 for women and 8.5 +/- 6.2 for men (ns). Clinical data including serological and hematological parameters and glandular and extraglandular manifestations were compared between men and women. Results: Male patient serology was characterized by more frequent positivity for anti-Ro/SSA and anti-La/SSB (p = 0. 02), and ANA (p = 0.02). Further, men with pSS were more frequently diagnosed with interstitial lung disease (p = 0. 008), lymphadenopathy (p = 0.04) and lymphoma (p = 0.007). Conversely, concomitant hypothyroidism was more common among female patients (p = 0.009). Conclusions: We observe enhanced serological responses and higher frequencies of lymphoma-related extraglandular manifestations in men with pSS. Notably, lymphoma itself was also significantly more common in men. These observations may reflect an aggravated immune activation and a more severe pathophysiological state in male patients with pSS and indicate a personalized managing of the disease due to the influence of the sex of patients with pSS., Funding Agencies|Swedish Research Council; Heart-Lung Foundation; Stockholm County Council; Karolinska Institutet; Swedish Rheumatism association; King Gustaf the Vth 80-year foundation; AstraZeneca Science for Life Laboratory Research Collaboration grant

Published
2017
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28. MAMA ROSA.

Author

BUCHER, SARA

Published
2020

29. TERMINAL.

Author

BUCHER, SARA

Published
2020

30. Microvascular response in the ECRB muscle of patients with lateral epicondylitis

Author

Oskarsson, Eva, Bucher, Sara, Söderlund, Karin, Pettersson, Kurt, Piehl Aulin, Karin, Oskarsson, Eva, Bucher, Sara, Söderlund, Karin, Pettersson, Kurt, and Piehl Aulin, Karin

Abstract

The microvascular response in extensor carpi radialis brevis (ECRB) muscle was studied in thirteen patients with unilateral epicondylitis. At rest the intramuscular blood flow was significantly lower in the affected arm than in the unaffected (P = 0.006). During dorsal extension for 1 min at 40% maximal voluntary contraction (MVC) and 2 min at 20% MVC, blood flow increased significantly in both arms (P = 0.02). Microcirculation remained above resting level both 1 and 2 min after contraction at 40% MVC but was back to the precontraction level 2 min after contraction at 20 % MVC. The reactive hyperaemic response after occlusion of the brachial artery for 5 min, showed no significant difference between the arms. The reason for the hampered microcirculation in ECRB at rest does not seem to be due to a decreased ability of the vessel wall to dilate. Other plausible reasons merits further investigation.

31. Intramuscular pressure in the ECRB muscle of patients with lateral epicondylitis

Author

Oskarsson, Eva, Piehl Aulin, Karin, Hurtig Wennlöf, Anita, Bucher, Sara, Söderlund, Karin, Pettersson, Kurt, Oskarsson, Eva, Piehl Aulin, Karin, Hurtig Wennlöf, Anita, Bucher, Sara, Söderlund, Karin, and Pettersson, Kurt

Abstract

An increased tension and a low intramuscular blood flow in the extensor carpi radialis (ECRB) muscle in patient with lateral epichondylitis has been suggested to contribute to the symptoms. The reason for the lower blood flow may be increased intramuscular pressure. The purpose of this pilot study was to determine intramuscular pressure and blood flow in affected and unaffected ECRB in ten patients with unilateral epicondylitis, with a mean duration of symptoms of 24 (13-48) months. Intramuscular pressure (IMP) was measured using the microcapillary infusion technique and intramuscular blood flow using the laser Doppler flowmetry technique, bilaterally with the non-affected arm serving as a control. The recordings were performed at rest, during isometric dorsal extension of the wrist for 1 min at 40 % and 2 min at 20 % of maximal voluntary contraction (MVC) and during recovery after contractions. At rest the median IMP was 7-8 mm Hg regardless of arm while the median intramuscular blood flow was lower on the affected side compared with the unaffected side (P=0.03). During contraction the IMP and blood flow increased regardless of arm. The IMP fell to pre-contraction level within 2 s after contraction, independent of arm and contraction force. Recovery, regarding the intramuscular blood flow, tended to be faster on the unaffected side than on the affected after contraction at 20 % MVC. After contraction at 40 % MVC the blood flow was equal on both sides. When the IMP value in the unaffected muscle was corrected for the higher force elicited compared to affected muscle the adjusted IMP was significantly lower (P=0.006) at 20 % MVC. In summary, affected ECRB has a lower intramuscular blood flow during rest and a higher intramuscular pressure in relation to the unaffected muscle at contraction for 2 min at 20 % MVC.

32. Thiourea-based rotaxanes: anion transport across synthetic lipid bilayers and antibacterial activity against Staphylococcus aureus .

Author

Akhtar N, Conthagamage UNK, Bucher SP, Abdulsalam ZA, Davis ML, Beavers WN, and García-López V

Abstract

We report the synthesis of two rotaxanes (1 and 2) whose rings have appended thiourea units for the selective recognition of Cl - anions. Rotaxane 1 transports Cl - across synthetic lipid bilayers more efficiently than 2, exhibiting EC 50 values of 0.243 mol% versus 0.736 mol%, respectively. A control rotaxane (3) without the thiourea units and the individual axle (4) also showed Cl - transport, although with much lower efficiency (EC 50 values of 4.044 mol% and 4.986 mol%). The unthreaded ring (5) showed the lowest transport activity. This trend highlights the advantage of the interlocked system with a ring containing thiourea units. We also investigated how the membrane composition of liposomes influences the transport activity of 1 and 2, observing higher Cl - transport in membranes with higher fluidity. Additionally, we demonstrated that rotaxane 1 can kill drug-resistant and osmotolerant Staphylococcus aureus when used in combination with NaCl or arachidonic acid. The latter is known to increase the fluidity of the membrane in S. aureus , highlighting cooperative behavior. This work provides new insights into how various structural features and the membrane environment influence the anion transport activity of rotaxanes, offering important design principles for optimizing future rotaxanes for biomedical and other applications., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Published
2024
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33. Unraveling The Genetics of Shared Clinical and Serological Manifestations in Systemic Inflammatory Autoimmune Diseases.

Author

Bianchi M, Kozyrev SV, Notarnicola A, Sandling JK, Pettersson M, Leonard D, Sjöwall C, Gunnarsson I, Rantapää-Dahlqvist S, Bengtsson AA, Jönsen A, Svenungsson E, Enocsson H, Kvarnström M, Forsblad-d'Elia H, Magnusson Bucher S, Norheim KB, Baecklund E, Jonsson R, Hammenfors D, Eriksson P, Mandl T, Omdal R, Padyukov L, Andersson H, Molberg Ø, Pyndt Diederichsen L, Syvänen AC, Wahren-Herlenius M, Nordmark G, Lundberg IE, Rönnblom L, and Lindblad-Toh K

Abstract

Objectives: Systemic inflammatory autoimmune diseases (SIADs) such as systemic lupus erythematosus (SLE), primary Sjögren's syndrome (pSS) and idiopathic inflammatory myopathies (myositis) are complex conditions characterized by shared circulating autoantibodies and clinical manifestations, including skin rashes, among others. This study aimed at elucidating the genetics underlying these common features., Methods: We performed targeted DNA sequencing of coding and regulatory regions from ~1,900 immune-related genes in a large SIAD cohort of 2,292 well-characterized Scandinavian patients with SLE, pSS and myositis, as well as 1,252 controls. A gene-based functionally-weighted genetic score for aggregate testing of all genetic variants, including rare variants, was complemented by in-silico functional analyses and in-vitro reporter experiments., Results: Case-control association analysis detected known and potentially novel genetic loci in agreement with previous genetic and transcriptomics findings linked to the SIAD autoimmune background. Intriguingly, case-case comparisons between patient subgroups with and without specific autoantibodies revealed that the subgroups defined by ANA and anti-dsDNA antibodies have unique genetic profiles reflecting their heterogeneity. When focusing on clinical features, we overall showed that DUSP1 protective genetic variants lead to increased gene expression and potentially to anti-inflammatory effects on the SIAD-associated skin phenotype. This is consistent with recent genetic findings on eczema and with the previously reported downregulation of the MAPK signaling-related gene DUSP1 in other skin disorders., Conclusion: Together, this suggests common molecular mechanisms potentially underlying overlapping clinical manifestations shared among different disorders and informs clinical heterogeneity, which could be translated to improve disease diagnostic and treatment, also in more generalized disease frameworks., (This article is protected by copyright. All rights reserved.)

Published
2024
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34. Variants in the DDX6-CXCR5 autoimmune disease risk locus influence the regulatory network in immune cells and salivary gland.

Author

Wiley MM, Khatri B, Joachims ML, Tessneer KL, Stolarczyk AM, Rasmussen A, Anaya JM, Aqrawi LA, Bae SC, Baecklund E, Björk A, Brun JG, Bucher SM, Dand N, Eloranta ML, Engelke F, Forsblad-d'Elia H, Fugmann C, Glenn SB, Gong C, Gottenberg JE, Hammenfors D, Imgenberg-Kreuz J, Jensen JL, Johnsen SJA, Jonsson MV, Kelly JA, Khanam S, Kim K, Kvarnström M, Mandl T, Martín J, Morris DL, Nocturne G, Norheim KB, Olsson P, Palm Ø, Pers JO, Rhodus NL, Sjöwall C, Skarstein K, Taylor KE, Tombleson P, Thorlacius GE, Venuturupalli S, Vital EM, Wallace DJ, Grundahl KM, Radfar L, Brennan MT, James JA, Scofield RH, Gaffney PM, Criswell LA, Jonsson R, Appel S, Eriksson P, Bowman SJ, Omdal R, Rönnblom L, Warner BM, Rischmueller M, Witte T, Farris AD, Mariette X, Shiboski CH, Wahren-Herlenius M, Alarcón-Riquelme ME, Ng WF, Sivils KL, Guthridge JM, Adrianto I, Vyse TJ, Tsao BP, Nordmark G, and Lessard CJ

Abstract

Fine mapping and bioinformatic analysis of the DDX6-CXCR5 genetic risk association in Sjögren's Disease (SjD) and Systemic Lupus Erythematosus (SLE) identified five common SNPs with functional evidence in immune cell types: rs4938573, rs57494551, rs4938572, rs4936443, rs7117261. Functional interrogation of nuclear protein binding affinity, enhancer/promoter regulatory activity, and chromatin-chromatin interactions in immune, salivary gland epithelial, and kidney epithelial cells revealed cell type-specific allelic effects for all five SNPs that expanded regulation beyond effects on DDX6 and CXCR5 expression. Mapping the local chromatin regulatory network revealed several additional genes of interest, including lnc-PHLDB1-1 . Collectively, functional characterization implicated the risk alleles of these SNPs as modulators of promoter and/or enhancer activities that regulate cell type-specific expression of DDX6 , CXCR5 , and lnc-PHLDB1-1 , among others. Further, these findings emphasize the importance of exploring the functional significance of SNPs in the context of complex chromatin architecture in disease-relevant cell types and tissues., Competing Interests: Competing Interests C.J.L.* and A.D.F. have an active collaborative research agreement with Janssen. E.B. has an active research collaboration with Pfizer. T.M. is employed as medical solutions lead in rheumatology at UCB. R.H.S. is a consultant for Jansen Pharmaceuticals. S.J.B. provided consultancy services for Abbvie, BMS, Galapagos, Iqvia, J&J, Kiniksa, and Novartis in 2020–2021. L.R. provided consultancy services for AstraZeneca. B.M.W. has active collaborative research agreements with Astellas Bio and Pfizer, Inc. M.R. received grants from Amgen, AstraZeneca, Bristol Myers-Squibb, Novartis, and Servier for clinical trials in Sjögren’s Syndrome and SLE. All other authors have reported that they have no competing interests to report.

Published
2023
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35. Rare X Chromosome Abnormalities in Systemic Lupus Erythematosus and Sjögren's Syndrome.

Author

Sharma R, Harris VM, Cavett J, Kurien BT, Liu K, Koelsch KA, Fayaaz A, Chaudhari KS, Radfar L, Lewis D, Stone DU, Kaufman CE, Li S, Segal B, Wallace DJ, Weisman MH, Venuturupalli S, Kelly JA, Pons-Estel B, Jonsson R, Lu X, Gottenberg JE, Anaya JM, Cunninghame-Graham DS, Huang AJW, Brennan MT, Hughes P, Alevizos I, Miceli-Richard C, Keystone EC, Bykerk VP, Hirschfield G, Nordmark G, Bucher SM, Eriksson P, Omdal R, Rhodus NL, Rischmueller M, Rohrer M, Wahren-Herlenius M, Witte T, Alarcón-Riquelme M, Mariette X, Lessard CJ, Harley JB, Ng WF, Rasmussen A, Sivils KL, and Scofield RH

Subjects
Alleles, Bayes Theorem, Female, Gene Dosage, Humans, Karyotype, Lupus Erythematosus, Systemic epidemiology, Polymorphism, Single Nucleotide, Sex Chromosome Disorders of Sex Development epidemiology, Sex Chromosome Disorders of Sex Development genetics, Sjogren's Syndrome epidemiology, Trisomy genetics, Turner Syndrome epidemiology, Turner Syndrome genetics, Chromosomes, Human, X genetics, Lupus Erythematosus, Systemic genetics, Mosaicism statistics & numerical data, Sex Chromosome Aberrations statistics & numerical data, Sjogren's Syndrome genetics
Abstract

Objective: Sjögren's syndrome (SS) and systemic lupus erythematosus (SLE) are related by clinical and serologic manifestations as well as genetic risks. Both diseases are more commonly found in women than in men, at a ratio of ~10 to 1. Common X chromosome aneuploidies, 47,XXY and 47,XXX, are enriched among men and women, respectively, in either disease, suggesting a dose effect on the X chromosome., Methods: We examined cohorts of SS and SLE patients by constructing intensity plots of X chromosome single-nucleotide polymorphism alleles, along with determining the karyotype of selected patients., Results: Among ~2,500 women with SLE, we found 3 patients with a triple mosaic, consisting of 45,X/46,XX/47,XXX. Among ~2,100 women with SS, 1 patient had 45,X/46,XX/47,XXX, with a triplication of the distal p arm of the X chromosome in the 47,XXX cells. Neither the triple mosaic nor the partial triplication was found among the controls. In another SS cohort, we found a mother/daughter pair with partial triplication of this same region of the X chromosome. The triple mosaic occurs in ~1 in 25,000-50,000 live female births, while partial triplications are even rarer., Conclusion: Very rare X chromosome abnormalities are present among patients with either SS or SLE and may inform the location of a gene(s) that mediates an X dose effect, as well as critical cell types in which such an effect is operative., (© 2017, American College of Rheumatology.)

Published
2017
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36. Long-term follow-up in primary Sjögren's syndrome reveals differences in clinical presentation between female and male patients.

Author

Ramírez Sepúlveda JI, Kvarnström M, Eriksson P, Mandl T, Norheim KB, Johnsen SJ, Hammenfors D, Jonsson MV, Skarstein K, Brun JG, Rönnblom L, Forsblad-d'Elia H, Magnusson Bucher S, Baecklund E, Theander E, Omdal R, Jonsson R, Nordmark G, and Wahren-Herlenius M

Subjects
Autoantibodies metabolism, Biomarkers blood, Comorbidity, Female, Follow-Up Studies, Humans, Male, Middle Aged, Severity of Illness Index, Sjogren's Syndrome complications, Sjogren's Syndrome diagnosis, Sjogren's Syndrome physiopathology
Abstract

Background: Despite men being less prone to develop autoimmune diseases, male sex has been associated with a more severe disease course in several systemic autoimmune diseases. In the present study, we aimed to investigate differences in the clinical presentation of primary Sjögren's syndrome (pSS) between the sexes and establish whether male sex is associated with a more severe form of long-term pSS., Methods: Our study population included 967 patients with pSS (899 females and 68 males) from Scandinavian clinical centers. The mean follow-up time (years) was 8.8 ± 7.6 for women and 8.5 ± 6.2 for men (ns). Clinical data including serological and hematological parameters and glandular and extraglandular manifestations were compared between men and women., Results: Male patient serology was characterized by more frequent positivity for anti-Ro/SSA and anti-La/SSB (p = 0.02), and ANA (p = 0.02). Further, men with pSS were more frequently diagnosed with interstitial lung disease (p = 0.008), lymphadenopathy (p = 0.04) and lymphoma (p = 0.007). Conversely, concomitant hypothyroidism was more common among female patients (p = 0.009)., Conclusions: We observe enhanced serological responses and higher frequencies of lymphoma-related extraglandular manifestations in men with pSS. Notably, lymphoma itself was also significantly more common in men. These observations may reflect an aggravated immune activation and a more severe pathophysiological state in male patients with pSS and indicate a personalized managing of the disease due to the influence of the sex of patients with pSS.

Published
2017
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37. Use of biologic agents in idiopathic inflammatory myopathies in Sweden: a descriptive study of real life treatment.

Author

Svensson J, Holmqvist M, Tjärnlund A, Dastmalchi M, Hanna B, Magnusson Bucher S, and Lundberg IE

Subjects
Adolescent, Aged, Anti-Inflammatory Agents adverse effects, Biological Products adverse effects, Drug Substitution, Female, Humans, Interleukin 1 Receptor Antagonist Protein therapeutic use, Male, Middle Aged, Myositis diagnosis, Myositis epidemiology, Myositis immunology, Off-Label Use, Registries, Rituximab therapeutic use, Sweden epidemiology, Time Factors, Treatment Outcome, Tumor Necrosis Factor-alpha antagonists & inhibitors, Tumor Necrosis Factor-alpha immunology, Young Adult, Anti-Inflammatory Agents therapeutic use, Biological Products therapeutic use, Myositis drug therapy
Abstract

Objectives: Biologic treatment has revolutionised treatment in rheumatology in the last decades. Patients with idiopathic inflammatory myopathies (IIM) have so far only been treated with biologics off-label, with little published follow-up on those who are treated and how they are treated. We therefore set out to characterise the Swedish IIM patients who have been treated with biologics., Methods: By linking Swedish registers we identified 95 patients with IIM who were treated with biologics between 2000 and 2011. Via chart review the diagnoses were validated and clinical characteristics extracted., Results: In total, 95 individuals with IIM and biologic treatment were identified. Median disease duration was 5.5 years at start of biologics. All patients had been treated with prednisolone and failed at least one previous DMARD before the start of first biologic. Rituximab was the most common biologic drug, followed by anakinra and TNFinhibitors. Median overall treatment length was 10 months and varied between 5 and 12.5 months or the different therapies., Conclusions: Off-label treatment of IIMs is often tried and seldom successful. This study shows a large unmet need for novel treatments and therapies in IIM. It is therefore important to follow these patients in a structured way to learn about effects and potential risks for different subgroups of IIM associated with different therapies.

Published
2017

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