Immunofixation as a Diagnostic Method for Multiple Myeloma - PDF

Immunofixation as a diagonstic method for Multiple myeloma subtypes Done by: Fatma Naif Mohsin Supervised by: Dr. Shoroq Abdul-Razzak Hassan  Introduction Epidemiology Risk factors Table of Clinical features contents Lab tests Immunofixation...

Immunofixation as a diagonstic method for Multiple myeloma subtypes Done by: Fatma Naif Mohsin Supervised by: Dr. Shoroq Abdul-Razzak Hassan  Introduction Epidemiology Risk factors Table of Clinical features contents Lab tests Immunofixation Treatment Introduction Epidemiology 2nd most cause of The exact cause is hematological The median age unknown. malignancies for diagnosis >70 after NHL. High rate Males: Females incidence in (2:1) Africans than Caucasians Risk factor Risk factor Chromosomal abnormalities - 80% of patients have chromosomal abnormalities detected by FISH analysis, with the remaining 20% having genetic abnormalities detected by gene expression profiling and special karyotyping, both of them resulting in abnormal regulation of intracellular signaling pathways. - Translocation of the Igs heavy chain on chromosome 14 and the cyclin D1 gene on chromosome 11, which cause uncontrolled secretions - Deletion of chromosome 13 & 10 - Short arm deletion of chromosome 17 is one of the major abnormalities that impair the survival of patients Clinical features CRAB criteria Hypercalcemia Due to the interaction between myeloma cells & the bone microenvironment, which causes increase in the osteoclast activity which is responsible for degrading bones. This hyperactivity is caused by cytokines secretions like RANK-L, MIP-1α, DKK1, IL-6.  Renal impairment is due to many factors, one of them being increase in the Ca2+ levels. Also, accumulation of Bence Jones proteins & Amyloid deposition causes tubular obstruction. Renal M proteins form crystalline inclusions, and the patient will also show Nephrotoxicity. dysfunction And we’ll notice electrolytes imbalance. Using NSAIDs will also cause kidney damage.  Normocytic & Normochromic. Due to infiltration of bone marrow, and inhibition in hematopoiesis by cytokines like IL-1 & TNFs which suppress erythropoiesis. Kidney dysfunction leads to reduce erythropoietin production that will also contribute with the decrease Anemia in RBCs production. Pancytopenia is also noticed in MM pateins.  The increase in the activation of osteoclasts & inhibition of the osteoblast caused by the stimulation of myeloma cells leads to increase in bone resorption, resulting in lytic lesions particularly in the skull, ribs, spine & long bones. Bone Lytic lesions & the decrease in bone density will lead to pathological fracture in case of any minimal lesions trauma. Non-CRAB features Recurrent infections Despite having high levels of one of the Igs, the patient will have hypoglobulinemia in the other Igs caused by the defect of B cells which is going to decrease the humoral immunity making the patient more susceptible to bacterial infection, such as S.aureus & S.pneumonia, that will often lead to pneumonia, pyelonephritis & septicemia. Crygrobulinemia Which is caused by perception of Igs at temperature below 37°C that will lead to clumping of blood and causes Raynaud's phenomenon, thrombosis & gangrene the extremities Non-CRAB features Hyperviscosity syndrome It’s one of the rare manifestations of MM, caused by the overproduction of IgG1, IgG3 or IgA. It will cause thickness of blood, and the patient will show symptoms of vertigo, shortness of breath, epistaxis, loss of vision, hypertension Lethargy MM subtypes Based on the Igs heavy chains & light chains: - IgGκ or IgGλ - IgAκ or IgAλ - IgMκ or IgMλ - IgEκ or IgEλ - IgDκ or IgDλ - Light chains only (Bence Jones myeloma) Lab findings Serum Protein Electrophoresis It’s an important diagnostic method for quantifying M proteins. Principle: separation of charged solutes of particles in a liquid medium under the influence of the electrical field, based on their size & molecular wight. Increase in the Gamma band means high paraproteins levels & it’s known as “M spike” Immunofixation It’s a method that used to differentiate between the Igs and their light chains It consists of two phases: Electrophoresis & Fixation. Principle: Perception by adding Abs to the sample that bind to Ags forming Ag-Ab complex. Procedure ❑Electrophoreses phase Separation of paraproteins under electrical charged field based on their size. ❑Fixation phase Adding specific antisera for the heavy chains G,A,M,D,E and light chains kappa & lamda Advantages of IFE High specificity for detecting specific proteins. High sensitivity for identifying low concentration proteins. Differentiate between paraproteins types. Monitoring disease prognosis. Management for treatment. Treatment Chemotherapy. Steroid therapy. Stem cell Radiation therapy. transplantation. THANK YOU