**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.**
Stephan Settelmeier, Department of Cardiology and Vascular Medicine, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

**Main Body of the Abstract**
Background: Cardiac amyloidosis is a myocardial storage disorder in which deposits of misfolded mono- or oligomers of the serum protein transthyretin (TTR) trigger a progressive amyloid cardiomyopathy (ATTR-CM). Naturally occurring autoantibodies (nAbs) are defined as germline-encoded autoreactive immunoglobulins found in individuals without (known) prior antigen exposure. A role of nAbs has been described in several neurodegenerative diseases. NAbs have not yet been described in cardiac storage diseases.
Objective: To identify nAbs in ATTR-CM and assess their role as biomarker in diagnosis and monitoring of disease progression and treatment as there is currently no established specific biomarker for ATTR-CM.
Material & Methods: Serum from healthy donors as well as umbilical cord blood and pooled donor immunoglobins were tested for IgM and IgG antibodies against recombinant wild-type TTR, recombinant V122I-variant, recombinant L55P-variant and native TTR in fibrillar and non-fibrillar form by ELISA and dot-blot protein analysis.
Results: NAbs of the IgM type against TTR are already detectable in the umbilical cord blood. The titers differ from those of adult donors. There is no loss of detection in the fibrillar TTR form. The responsible B-cell fraction of TTR-specific IgM could be detected.
Summary & Conclusion: NAbs of the IgM type against various TTR forms were detected. Their significance is currently unclear, thus underlining the importance of further investigations.



**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.**
Stephan Settelmeier, Department of Cardiology and Vascular Medicine, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

**Main Body of the Abstract**
**Background**: Cardiac amyloidosis is a myocardial storage disorder in which deposits of misfolded mono- or oligomers of the serum protein transthyretin (TTR) trigger a progressive amyloid cardiomyopathy (ATTR-CM). Naturally occurring autoantibodies (nAbs) are defined as germline-encoded autoreactive immunoglobulins found in individuals without (known) prior antigen exposure. A role of nAbs has been described in several neurodegenerative diseases. NAbs have not yet been described in cardiac storage diseases.
**Objective**: To identify nAbs in ATTR-CM and assess their role as biomarker in diagnosis and monitoring of disease progression and treatment as there is currently no established specific biomarker for ATTR-CM.
**Material & Methods**: Serum from healthy donors as well as umbilical cord blood and pooled donor immunoglobins were tested for IgM and IgG antibodies against recombinant wild-type TTR, recombinant V122I-variant, recombinant L55P-variant and native TTR in fibrillar and non-fibrillar form by ELISA and dot-blot protein analysis.
**Results**: NAbs of the IgM type against TTR are already detectable in the umbilical cord blood. The titers differ from those of adult donors. There is no loss of detection in the fibrillar TTR form. The responsible B-cell fraction of TTR-specific IgM could be detected.
**Summary & Conclusion**: NAbs of the IgM type against various TTR forms were detected. Their significance is currently unclear, thus underlining the importance of further investigations.



Naturally occurring antibodies as biomarker for cardiac ATTR amyloidosis PB12 (#337)

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.