Calreticulin’s Role(s) in Autoimmune Disorders

Sontheimer, Richard D.; Racila, Doina; Racila, Emil; Eggleton, Paul; Donnelly, Suzanne

doi:10.1007/978-1-4419-9258-1_17

Cited by 5 publications

(4 citation statements)

References 45 publications

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“…CD93 (C1qRp) has recently been shown in knockout mice to contribute to the removal of apoptotic cells in vivo but is not required for C1q-mediated enhancement of phagocytosis (Norsworthy et al, 2004). And interestingly, the cC1q-R receptor has been shown to be virtually identical in amino acid sequence to calreticulin, a highly conserved, multifunctional, calcium-binding human autoantigen that has been a major focus of our lab in the past (McCauliffe et al, 1990;Cheng et al, 1996;Sontheimer et al, 2003). Whether calreticulin autoantibodies (AAB) might interfere with cC1q receptor function has yet to be examined.…”

Section: Interaction Of C1q With Receptorsmentioning

confidence: 96%

“…The relationship between calreticulin and the Ro/S-A ribonucleoprotein autoantigen, however, has proved to be a complex one that has yet to be fully characterized (Cheng et al, 1996;Lieu and Sontheimer, 1997;Sontheimer et al, 2003). Subsequent work has shown that calreticulin AAB detectible by solid-phase immunoassay can be found in a number of other clinical settings that are not closely related to the Ro/SS-A autoimmune response (e.g., celiac disease, rheumatoid arthritis, primary biliary cirrhosis, autoimmune hepatitis, halothane hepatitis, schistosomiasis, trypanosomiasis, leishmaniasis) .…”

Section: Interaction Of C1q With Other Protein Classesmentioning

confidence: 98%

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C1q: Its Functions within the Innate and Adaptive Immune Responses and its Role in Lupus Autoimmunity

Sontheimer

Racila

2005

Journal of Investigative Dermatology

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The complement cascade is a multi-faced effector component of the innate immune response. C1q is the recognition component of the classical pathway of complement activation. In addition, C1q has been recognized to serve a number of other biological functions including a modulating role on cellular functions within the adaptive immune response. The importance of C1q to normal immune regulation is reflected by the fact that greater than 90% of individuals who have complete congenital deficiency of C1q have been observed to develop early-onset photosensitive systemic lupus erythematosus (SLE). As a number of single nucleotide polymorphisms have been identified in three C1q genes, it is possible that more subtle variations in C1q expression could be a risk factor for cutaneous LE and SLE. Thus, a more comprehensive delineation of complotype could be of increasing clinical importance in the future.

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Section: Interaction Of C1q With Receptorsmentioning

confidence: 96%

Section: Interaction Of C1q With Other Protein Classesmentioning

confidence: 98%

C1q: Its Functions within the Innate and Adaptive Immune Responses and its Role in Lupus Autoimmunity

Sontheimer

Racila

2005

Journal of Investigative Dermatology

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“…Further studies showed that subcutaneous inoculation of recombinant CRT fragment into nude mice not only prevented the development of subcutaneous tumors, but also inhibited the growth of established ones (Tosato et al, 2003 ). Since the collagen tail of C1q (cC1q) binds to the N-terminal half of cC1qR/CRT, which contains several short (7–10 amino acids) CH2-like motifs (ExKxKx) similar to the C1q binding motif found in the CH2 domain of IgG (Sontheimer et al, 2003 ), these C1q binding regions of cC1qR/CRT have the potential to be developed into therapeutic modalities.…”

Section: The Emerging Role Of C1q In Carcinogenesismentioning

confidence: 99%

The C1q Family of Proteins: Insights into the Emerging Non-Traditional Functions

Ghebrehiwet¹,

Hosszu²,

Valentino³

et al. 2012

Front. Immun.

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Research conducted over the past 20 years have helped us unravel not only the hidden structural and functional subtleties of human C1q, but also has catapulted the molecule from a mere recognition unit of the classical pathway to a well-recognized molecular sensor of damage-modified self or non-self antigens. Thus, C1q is involved in a rapidly expanding list of pathological disorders – including autoimmunity, trophoblast migration, preeclampsia, and cancer. The results of two recent reports are provided to underscore the critical role C1q plays in health and disease. First is the observation by Singh et al. (2011) showing that pregnant C1q−/− mice recapitulate the key features of human preeclampsia that correlate with increased fetal death. Treatment of the C1q−/− mice with pravastatin restored trophoblast invasiveness, placental blood flow, and angiogenic balance and, thus, prevented the onset of preeclampsia. Second is the report by Hong et al. (2009) which showed that C1q can induce apoptosis of prostate cancer cells by activating the tumor suppressor molecule WW-domain containing oxydoreductase (WWOX or WOX1) and destabilizing cell adhesion. Downregulation of C1q on the other hand, enhanced prostate hyperplasia and cancer formation due to failure of WOX1 activation. C1q belongs to a family of structurally and functionally related TNF-α-like family of proteins that may have arisen from a common ancestral gene. Therefore C1q not only shares the diverse functions with the tumor necrosis factor family of proteins, but also explains why C1q has retained some of its ancestral “cytokine-like” activities. This review is intended to highlight some of the structural and functional aspects of C1q by underscoring the growing list of its non-traditional functions.

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“…However, following a period of controversy it was demonstrated that calreticulin was not the primary autoantigenic 60 kDa Ro/SS-A polypeptide (22,23). The basis for this controversy has been previously reviewed (24).…”

Section: Molecular Characterization Of the Ro/ss-a Autoantigenmentioning

confidence: 99%

James Neil Gilliam, MD—the career arc of a patient-oriented translational clinical investigation changemaker in rheumatologic skin disease

Sontheimer

2018

Ann. Transl. Med

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James Neil Gilliam, MD, was an American academic physician who was trained in internal medicine, dermatology, dermatopathology and rheumatology. This "quadruple-threat" profile of postgraduate medical training provided him with a rather unique perspective on genetically-complex, environmentally-impacted human autoimmune disorders such as lupus erythematosus (LE). Both the skin and vital internal organs can be damaged by LE autoimmunity. And, LE is clinically-expressed quite variably from one individual to another making prognosis difficult. As such it can be very challenging to know what the optimal treatment approach might be for new patients presenting with this potentially-fatal disorder. Dr. Gilliam's major career focus was to better understand the complex relationships that exist between the clinical expression of LE in the skin and vital internal organs. In the late 1970s, Dr. Gilliam first described a new clinical form of LE skin disease that he designated as "subacute cutaneous LE." Subacute cutaneous LE would subsequently serve as the linchpin for a new classification scheme for LE skin disease that would later become known as the "Gilliam classification" of LE skin disease. In addition, he was among the first to apply modern immunologic insight to the classification of cutaneous LE. This work was carried out in the Divisions of Dermatology and Rheumatology and the Department of Dermatology at the University of Texas Southwestern Medical School in Dallas, Texas (UT Southwestern) starting in 1972. Dr. Gilliam served as the Founding Chairman of the Department of Dermatology at UT Southwestern in 1982, 2 years before his untimely death. Dr. Gilliam's clinical research accomplishments were matched by his ability to identify and encourage like-minded young people. A high percentage of his trainees went on to successful academic research careers and leadership positions in American Dermatology. Dr. Gilliam's untimely death from cancer deprived several generations of dermatologists and rheumatologists the benefit of his warm support and insightful guidance. In addition, American Dermatology and Rheumatology leadership organizations were deprived of his strong leadership skills.

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Calreticulin’s Role(s) in Autoimmune Disorders

Cited by 5 publications

References 45 publications

C1q: Its Functions within the Innate and Adaptive Immune Responses and its Role in Lupus Autoimmunity

C1q: Its Functions within the Innate and Adaptive Immune Responses and its Role in Lupus Autoimmunity

The C1q Family of Proteins: Insights into the Emerging Non-Traditional Functions

James Neil Gilliam, MD—the career arc of a patient-oriented translational clinical investigation changemaker in rheumatologic skin disease

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