**Author Listing - Lead/ Submitting Author (we will be communicating with this individual): Name, Institution, City and State where the work was done. Co-authors will be added in a separate section.**
Jakub Sikora, Department of Paediatrics and Inherited Metabolic Disorders, 1st Faculty of Medicine, Charles University, Prague, Czech Republic

**Main Body of the Abstract**
Serum amyloid A1 (SAA1) protein is one of the key acute (inflammatory) phase reactants. Amyloidosis A (AA) is a serious clinical condition resulting from systemic tissue deposition of SAA1 secondary to its serum/plasmatic elevation in various chronic inflammatory conditions.
We described a family with primary hereditary AA amyloidosis in 2021 (Sikora et al., Kidney International). Affected individuals developed proteinuria, chronic kidney disease and systemic deposition of amyloid composed of the SAA1.1 isoform. The phenotype associated with chr11:18287683 T>C (hg19) mutation in the SAA1 promoter in-cis to the amyloidogenic SAA1.1 haplotype. This genetic set up resulted in a doubling of the basal SAA1 promoter activity and sustained elevation of serum SAA levels. It segregated in an autosomal dominant pattern in 12 genetically affected and in none of 6 genetically unaffected relatives with a LOD score of >5. Tocilizumab had a beneficial effect in 4 affected family members.
We present therapeutic follow-up (5 years) data. The proband, unfortunately, died after the second kidney transplant. Treatment resulted in disappearance of proteinuria (nephrotic in one patient), stabilization of renal function and decrease of serum SAA concentrations below 10 mg/L in two patients. Despite the positive effect on renal function parameters, there is no satisfactory decrease in serum SAA in the third patient. A switch to Sarilumab, a human monoclonal IgG1 antibody specifically binding both the soluble and membrane-bound IL-6 receptor, is currently considered. One of the, so far, asymptomatic heterozygotes and his partner undergo clinical genetic counselling as a prerequisite for pre-implantation diagnostics.



**Author Listing - Lead/ Submitting Author (we will be communicating with this individual): Name, Institution, City and State where the work was done. Co-authors will be added in a separate section.**
Jakub Sikora, Department of Paediatrics and Inherited Metabolic Disorders, 1st Faculty of Medicine, Charles University, Prague, Czech Republic

**Main Body of the Abstract**
Serum amyloid A1 (SAA1) protein is one of the key acute (inflammatory) phase reactants. Amyloidosis A (AA) is a serious clinical condition resulting from systemic tissue deposition of SAA1 secondary to its serum/plasmatic elevation in various chronic inflammatory conditions.
We described a family with primary hereditary AA amyloidosis in 2021 (_Sikora et al., Kidney International_). Affected individuals developed proteinuria, chronic kidney disease and systemic deposition of amyloid composed of the SAA1.1 isoform. The phenotype associated with chr11:18287683 T>C (hg19) mutation in the _SAA1_ promoter _in-cis_ to the amyloidogenic _SAA1.1_ haplotype. This genetic set up resulted in a doubling of the basal _SAA1_ promoter activity and sustained elevation of serum SAA levels. It segregated in an autosomal dominant pattern in 12 genetically affected and in none of 6 genetically unaffected relatives with a LOD score of >5. Tocilizumab had a beneficial effect in 4 affected family members.
We present therapeutic follow-up (5 years) data. The proband, unfortunately, died after the second kidney transplant. Treatment resulted in disappearance of proteinuria (nephrotic in one patient), stabilization of renal function and decrease of serum SAA concentrations below 10 mg/L in two patients. Despite the positive effect on renal function parameters, there is no satisfactory decrease in serum SAA in the third patient. A switch to Sarilumab, a human monoclonal IgG1 antibody specifically binding both the soluble and membrane-bound IL-6 receptor, is currently considered. One of the, so far, asymptomatic heterozygotes and his partner undergo clinical genetic counselling as a prerequisite for pre-implantation diagnostics.



Hereditary AA Amyloidosis Caused by a Mutation in the SAA1 Promoter. Therapeutic Follow-up. PC84 (#139)

We invite you to attend the XIX International Symposium on Amyloidosis to be held in Rochester, MN.

This symposium is organized as a hybrid meeting (with the focus on in-person) held from Sunday, May 26 through Thursday, May 30, 2024.

Together with the ISA Board and members of Mayo Clinic, a very attractive scientific hybrid program is being planned. The program will cover a variety of types of systemic amyloidosis: ATTR (hereditary and wild-type), AL (light-chain), AA and less frequent forms. There will be key lectures, specific symposia including those company sponsored, oral presentations and poster sessions of accepted abstracts.

COURSE DESCRIPTION
This program will provide a comprehensive review of state-of-the-art education in systemic amyloidosis: basic science, pathophysiology, diagnosis, current and emerging treatments. Scientific presentations will include competitive oral and poster abstracts. The rapid evolution of scientific discovery and expanding treatment options has created tremendous interest in the field and this meeting will fill and important gap in educating scientists and clinicians.