Pyrin Antibodies

Pyrin (MEFV)

Involved in the regulation of innate immunity and the inflammatory response in response to IFNG/IFN-gamma. Organizes autophagic machinery by serving as a platform for the meeting of ULK1, Beclin 1/BECN1, ATG16L1, and ATG8 family members and recognizes specific autophagy targets, thus coordinating target recognition with meeting of the autophagic devices and initiation of autophagy.

Acts as an autophagy receptor for the degradation of several inflammasome components, including CASP1, NLRP1 and NLRP3, hence preventing excess IL1B- and IL18- mediated inflammation (PubMed:16785446, PubMed:17431422, PubMed:26347139). However, it may also have a beneficial impact in the inflammatory pathway.

Gene Information

Human
Gene Name:	MEFV
Uniprot:	O15553
Entrez:	4210

Family

Belongs to:
No superfamily

Alternative Names

FMF; FMFmarenostrin; Marenostrin; Mediterranean fever; MEFpyrin; MGC126560; MGC126586; TRIM20

Molecular Weight

Mass (kDA):
86.444 kDA

Genomic Context

Human
Location:	16p13.3
Sequence:	16; NC_000016.10 (3242027..3256776, complement)

Tissue Specificity

Expressed in peripheral blood leukocytes, particularly in mature granulocytes and to a lesser extent in monocytes but not in lymphocytes. Detected in spleen, lung and muscle, probably as a result of leukocyte infiltration in these tissues. Not expressed in thymus, prostate, testis, ovary, small intestine, colon, heart, brain, placenta, liver, kidney, pancreas. Expression detected in several myeloid leukemic, colon cancer, and prostate cancer cell lines.

Subcellular Localizations

[Isoform 1]: Cytoplasm, cytoskeleton. Cell projection, ruffle. Cell projection, lamellipodium. Nucleus. Cytoplasm. Cytoplasmic vesicle, autophagosome. Associated with microtubules and with the filamentous actin of perinuclear filaments and peripheral lamellar ruffles. In pre-apoptotic cells, colocalizes with PYCARD/ASC in large specks (inflammasomes). In migrating monocytes, strongly polarized at the leading edge of the cell where it colocalizes with polymerizing actin and PYCARD/ASC.; [Isoform 2]: Nucleus.

Diseases

• Familial Mediterranean Fever
• Brucellosis
• Amyloidosis
• Inflammation
• Arthritis
• Pain
• Asthma
• Abdominal Pain
• Serositis
• Pleurisy
• Airway Obstruction
• Hereditary Diseases

• Signs And Symptoms, Respiratory
• Amyloid Nephropathy
• Lung Diseases, Obstructive
• Secondary Amyloidosis
• Inflammatory Disorder
• Hereditary Autoinflammatory Diseases

Interacting Proteins

• CASP1
• PSTPIP1
• PYCARD

Pathways

• Pathogenesis
• Localization
• Inflammatory Response
• Secretion
• Aging
• Immune Response
• Reflex
• Innate Immune Response
• Lung Growth
• Cytokine Secretion
• Dna Methylation
• Methylation
• Transport

• Cell Adhesion
• Cell Migration
• Regulation Of Gene Expression
• Leukocyte Migration
• Response To Oxidative Stress
• Sensitization
• Response To Histamine

PTMs

• Cleavage
• Methylation

• Glycosylation
• Citrullination

For details, visit:
bosterbio.com/bosterbio-gene-info-cards/MEFV

Best Uses Of The MEFV Marker

The MEFV Marker (a relatively new gene) has been under intense scrutiny after recent findings that it is involved at the maturation IL18, and inflammasome activation. The gene is also implicated in PFAPA-like clinical presentation among patients with a variety inflammatory conditions. It is therefore crucial to identify patients with this genetic mutation.

MEFV must be present in order to activate inflammasome.

The pathogenic p.M694V mutation in MEFV triggers constitutive inflammasome activation, resulting in pyroptosis and increased IL-1b secretion in FMF patients. In healthy donors, Pyrin is inhibited by a second mechanism, whereas it is activated by MEFV phosphorylation/dephosphorylation in FMF patients. The Pyrin inflammasome activation is specifically triggered by the pathogenic p.M694V mutation in FMF patients. Colchicine, a superfamily inhibitor of PKC, also inhibits inflammation.

The results of the current study are important because the MEFV gene encodes Pyrin, a sensor for inflammasome activation. The relationship between MEFV mutants and Pyrin dysregulation is not well understood. Currently, the pathogenic p.M694V MEFV mutation results in constitutive activation of the Pyrin inflammasome in FMF patients, while the pathogenic p.M694V mutation leads to delayed apoptosis in FMF donors.

Researchers previously discovered that the MEFV gene is required for inflammasome stimulation in the melanoma cell strain U937. To activate inflammasome activation, these cells were stimulated using UCN-01 The MEFV gene was used to functionally identify the MEFV variant, p.M694V. Interestingly, a study from Boster Bio showed that p.M694V MEFV rendered U937 cells sensitive to UCN-01.

Inflammasome activation is the activation pro-caspase-1. The p32 and the p20 fragments of caspase-1 were created in mouse neutrophils. Inflammasome activation requires many steps. There are many components to the inflammasome and their genes. The adaptor protein binds to the sensor protein and forms tiny specks from the cytosol. These specks become active Caspase-1 dimers and activate IL-1b/IL-18.

This study provides additional insights into molecular mechanisms of inflammation in FMF patients. The genetic testing allows the researchers to determine which MEFV mutations are pathogenic. This reduces the uncertainty in the interpretation. These findings can also be used to develop effective therapeutic and diagnostic approaches for the disease.

MEFV is required for inflammasomal activation in boster bio and human neutrophils. Inflammasomes, multiprotein signaling platforms, mediate pivotal reactions in the innate immune response. NLRP3 is the most well-studied inflammasome proteins. The mechanism for NLRP3 assembly involves a two-step process, in which a lipopolysaccharide-induced increase in protein expression levels is followed by subsequent stimulation.

It is also required in order to make IL18.

CD patients have higher levels of genes that regulate inflammation, such as MEFV or NLRP3. These genes control the maturation of IL18. It is interesting that MEFV expression correlates well with other inflammatory markers such as IL-1b or NLRP3.

Mefv was expressed in both non-tumor and tumor tissue in the experiments. Additionally, Mefv/ mice had increased splenomegaly after the experiment, which indicates a higher level of systemic inflammation. Additionally, Mefv/ mice had significantly higher tumor burdens and splenomegaly at day 80 after AOM than WT mice. Histological analysis revealed that Mefv/ mice had epithelial hyperplasia.

MEFV plays a significant role in inflammatory intestinal disease (IBD), and is linked to an increased risk of developing colorectal carcinoma. It is also associated in hereditary Autoinflammatory Disease. Patients with this mutation also have increased MEFV expression in their colons. In mice, pyrin is implicated in maintaining intestinal homeostasis.

MEFV markers are required for IL18 maturation. In addition IL-18/IL-1b, neutrophils derived from patients with MEFV disease also secrete S100A12/caspase-1. However, healthy heterozygous MEFV-mutant carriers secrete significantly greater amounts of IL-18 then healthy heterozygous ones.

Expression of MEFV and NLRP3 were increased in inflamed colon tissues of Mefv-/ mice. Additionally, rIL18 improved colon inflammation and epithelial permeability. Moreover, rIL18 inhibits colon cancer development and decreases colon tumorigenesis. This gene is essential for the regulation of inflammation in mice. eBioscience Human FcR is a good option if you are looking for an inhibitor of the IL-18 gene.

MEFV is a genetically refractory inflammatory disease that results from mutations in the MEFV genes. The severity depends on the genotype, as well as the dose. The most severe clinical outcomes are associated with the M694V homozygous FEFV genotype. It is believed that neutrophils are involved in the inflammatory processes of FMF. Therefore, it was important for us to examine the activity in neutrophils from patients who had different MEFV genotypes. Isolated neutrophils from healthy individuals and disease controls were compared to those of patients with FMF.

It may lead to a PFAPA like clinical presentation

A mutation in an autoinflammatory gene causes PFAPA-like symptoms. Although the genetic background of PFAPA is unknown, patients with this condition often share many traits with those with other autoinflammatory disorders. Inflammasome-related genes may play a part in PFAPA's pathogenesis. The disorder has been found in a polygenic background, which indicates that it may be caused by environmental factors rather than by a single genetic mutation.

The primary cause of cyclic-fever in children is hyper-IgD (HIDS). The MVK gene, located on chromosome 12q24, is often mutated. This autosomal-recessive disorder is characterized not by the development of autoantibodies but rather episodes of chronic inflammation. HIDS affects about one third of Caucasians, mainly from western Europe. Approximately 60 percent of HIDS patients are Dutch or French. The clinical presentation of PFAPA as well as HIDS overlaps significantly.

Recurrent fevers can last from three to seven day. Approximately 25% of patients have a family history of recurrent fevers, which suggests that the condition runs in the family. 254 cases reported of PFAPA by November 2006 had been identified. The age of onset of fever was 2.8 years for the entire cohort. The rash was not common in the majority of patients.

Symptoms associated with PFAPA can be similar to aphthous stomatitis. In severe cases, the ulcers can last for several weeks. While PFAPA is more common than gingivitis, there are still some cases of periodontal disease and gingivitis. Several treatments have been developed to alleviate symptoms and reduce the risk of infection.

One study showed that PFAPA could be linked to heterozygous deletions in the SPAG7 genetic gene. This led to a lower incidence PFAPA. Patients in the treatment group were diagnosed with PFAPA after a longer period of time, and the duration of each episode was shorter. This may be due in part to the fact these patients presented with different clinical signs.

The use of colchicine for PFAPA has been associated with similar responses to other medications. The drug may reduce inflammation and alter lymphocyte adhesion. Colchicine is generally well tolerated. However, it can cause gastrointestinal symptoms. It may also cause lactose intolerance. However, MEFV mutants may have higher chances of experiencing gastrointestinal side reactions.

There are not many studies that have examined the effects of vitamin A on PFAPA. A 1989 study showed that tonsillectomy was very effective in four patients. Since then, many more studies were conducted. Mahamid and colleagues found that vitamin deficiency was associated to a significantly lower incidence and longer duration of febrile episodes. Both studies found that PFAPA syndrome resolved spontaneously within 6 months of treatment.